309374692019052020240522
1420-907176112019JunCellular and molecular life sciences : CMLSCell Mol Life SciAMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking.213321692133-216910.1007/s00018-019-03068-7To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength to extrinsic stimuli. This ability, termed synaptic plasticity, is at the heart of their function and is, thus, tightly regulated. In glutamatergic neurons, synaptic strength is controlled by the number and function of AMPA receptors at the postsynapse, which mediate most of the fast excitatory transmission in the central nervous system. Their trafficking to, at, and from the synapse, is, therefore, a key mechanism underlying synaptic plasticity. Intensive research over the last 20 years has revealed the increasing importance of interacting proteins, which accompany AMPA receptors throughout their lifetime and help to refine the temporal and spatial modulation of their trafficking and function. In this review, we discuss the current knowledge about the roles of key partners in regulating AMPA receptor trafficking and focus especially on the movement between the intracellular, extrasynaptic, and synaptic pools. We examine their involvement not only in basal synaptic function, but also in Hebbian and homeostatic plasticity. Included in our review are well-established AMPA receptor interactants such as GRIP1 and PICK1, the classical auxiliary subunits TARP and CNIH, and the newest additions to AMPA receptor native complexes.BissenDianeDInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.Max Planck Institute for Brain Research, Max von Laue Str. 4, 60438, Frankfurt am Main, Germany.FossFranziskaFInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.Acker-PalmerAmparoA0000-0002-8107-927XInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany. Acker-Palmer@bio.uni-frankfurt.de.Max Planck Institute for Brain Research, Max von Laue Str. 4, 60438, Frankfurt am Main, Germany. Acker-Palmer@bio.uni-frankfurt.de.Cardio-Pulmonary Institute (CPI), Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany. Acker-Palmer@bio.uni-frankfurt.de.engERC AdG 669742European Research CouncilInternationalCRC834Deutsche ForschungsgemeinschaftCRC1080Deutsche ForschungsgemeinschaftCRC1193Deutsche ForschungsgemeinschaftFOR2325Deutsche ForschungsgemeinschaftEXC 115Deutsche ForschungsgemeinschaftEXC 147Deutsche ForschungsgemeinschaftMax Plack Fellow ProgramMax-Planck-GesellschaftJournal ArticleReview20190401
SwitzerlandCell Mol Life Sci97054021420-682X0CNIH1 protein, human0Carrier Proteins0Egg Proteins0GRIP1 protein, human0Membrane Proteins0Nerve Tissue Proteins0Nuclear Proteins0PICk1 protein, human0Receptors, AMPA0TARP3KX376GY7LGlutamic AcidIMAnimalsCarrier ProteinsgeneticsmetabolismEgg ProteinsgeneticsmetabolismGene Expression RegulationGlutamic AcidmetabolismHumansMembrane ProteinsgeneticsmetabolismNerve NetphysiologyNerve Tissue ProteinsgeneticsmetabolismNeural Networks, ComputerNeuronal PlasticityphysiologyNeuronscytologymetabolismNuclear ProteinsgeneticsmetabolismProtein TransportReceptors, AMPAgeneticsmetabolismSynapsesmetabolismSynaptic TransmissionAMPA receptorsCNIHGRIP1MAGUKPICK1SynapseTARPTrafficking2018112920193720192122019436020195216020194360201941ppublish30937469PMC650278610.1007/s00018-019-03068-710.1007/s00018-019-03068-7Citri A, Malenka RC. Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008;33:18–41. doi: 10.1038/sj.npp.1301559.10.1038/sj.npp.130155917728696Bliss TVP, Collingridge GL, Morris RGM. Synaptic plasticity in health and disease: introduction and overview. Philos Trans R Soc B. 2013;369:2013029. doi: 10.1098/rstb.2013.0129.10.1098/rstb.2013.0129PMC384386324298133Turrigiano G. Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function. Cold Spring Harb Perspect Biol. 2012;4:1–17. doi: 10.1101/cshperspect.a005736.10.1101/cshperspect.a005736PMC324962922086977Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010;62:405–496. doi: 10.1124/pr.109.002451.10.1124/pr.109.002451PMC296490320716669Schwenk J, Baehrens D, Haupt A, Bildl W, Boudkkazi S, Roeper J, Fakler B, Schulte U. Regional diversity and developmental dynamics of the AMPA-receptor proteome in the mammalian brain. Neuron. 2014;84:41–54. doi: 10.1016/j.neuron.2014.08.044.10.1016/j.neuron.2014.08.04425242221Jacobi E, von Engelhardt J. Diversity in AMPAR complexes in the brain. Curr Opin Neurobiol. 2017;45:32–38. doi: 10.1016/j.conb.2017.03.001.10.1016/j.conb.2017.03.00128376410Schnell E, Sizemore M, Karimzadegan S, Chen L, Bredt DS, Nicoll RA. Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number. Proc Natl Acad Sci. 2002;99:13902–13907. doi: 10.1073/pnas.172511199.10.1073/pnas.172511199PMC12979512359873Rouach N, Byrd K, Petralia RS, Elias GM, Adesnik H, Tomita S, Karimzadegan S, Kealey C, Bredt DS, Nicoll RA. TARP γ-8 controls hippocampal AMPA receptor number, distribution and synaptic plasticity. Nat Neurosci. 2005;8:1525–1533. doi: 10.1038/nn1551.10.1038/nn155116222232Maher MP, Matta JA, Gu S, Seierstad M, Bredt DS. Getting a handle on neuropharmacology by targeting receptor-associated proteins. Neuron. 2017;96:989–1001. doi: 10.1016/j.neuron.2017.10.001.10.1016/j.neuron.2017.10.00129216460Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Müller CS, Bildl W, Baehrens D, Hüber B, Kulik A, Klöcker N, Schulte U, Fakler B. High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron. 2012;74:621–633. doi: 10.1016/j.neuron.2012.03.034.10.1016/j.neuron.2012.03.03422632720Bildl W, Haupt A, Müller CS, Biniossek ML, Thumfart JO, Hüber B, Fakler B, Schulte U. Extending the dynamic range of label-free mass spectrometric quantification of affinity purifications. Mol Cell Proteomics. 2012;11(M111):007955.PMC327774722067099Müller CS, Haupt A, Bildl W, Schindler J, Knaus H-G, Meissner M, Rammner B, Striessnig J, Flockerzi V, Fakler B, Schulte U. Quantitative proteomics of the Cav2 channel nano- environments in the mammalian brain. Proc Natl Acad Sci USA. 2010;107:14950–14957. doi: 10.1073/pnas.1005940107.10.1073/pnas.1005940107PMC293056920668236Greger IH, Watson JF, Cull-Candy SG. Structural and functional architecture of AMPA-type glutamate receptors and their auxiliary proteins. Neuron. 2017;94:713–730. doi: 10.1016/j.neuron.2017.04.009.10.1016/j.neuron.2017.04.00928521126Zhu S, Gouaux E. Structure and symmetry inform gating principles of ionotropic glutamate receptors. Neuropharmacology. 2017;112:11–15. doi: 10.1016/j.neuropharm.2016.08.034.10.1016/j.neuropharm.2016.08.034PMC508273327663701Henley JM, Wilkinson KA. Synaptic AMPA receptor composition in development, plasticity and disease. Nat Rev Neurosci. 2016;17:337–350. doi: 10.1038/nrn.2016.37.10.1038/nrn.2016.3727080385Jurado S. AMPA receptor trafficking in natural and pathological aging. Front Mol Neurosci. 2018;10:1–14. doi: 10.3389/fnmol.2017.00446.10.3389/fnmol.2017.00446PMC576724829375307Pick JE, Ziff EB. Regulation of AMPA receptor trafficking and exit from the endoplasmic reticulum. Mol Cell Neurosci. 2018;91:3–9. doi: 10.1016/j.mcn.2018.03.004.10.1016/j.mcn.2018.03.004PMC612877729545119Dong H, O’Brien RJ, Fung ET, Lanahan AA, Worley PF, Huganir RL. GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature. 1997;386:279–284. doi: 10.1038/386279a0.10.1038/386279a09069286Srivastava S, Osten P, Vilim FS, Khatri L, Inman G, States B, Daly C, Desouza S, Abagyan R, Valtschanoff JG, Weinberg RJ, Ziff EB. Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Cell. 1998;21:581–591.9768844Xia J, Zhang X, Staudinger J, Huganir RL. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron. 1999;22:179–187. doi: 10.1016/S0896-6273(00)80689-3.10.1016/S0896-6273(00)80689-310027300Brückner K, Labrador JP, Scheiffele P, Herb A, Seeburg PH, Klein R. EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron. 1999;22:511–524. doi: 10.1016/S0896-6273(00)80706-0.10.1016/S0896-6273(00)80706-010197531Dong H, Zhang P, Song I, Petralia RS, Liao D, Huganir RL. Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2. J Neurosci. 1999;19:6930–6941. doi: 10.1523/JNEUROSCI.19-16-06930.1999.10.1523/JNEUROSCI.19-16-06930.1999PMC678285110436050Setou M, Seog DH, Tanaka Y, Kanai Y, Takei Y, Kawagishi M, Hirokawa N. Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Nature. 2002;417:83–87. doi: 10.1038/nature743.10.1038/nature74311986669Hoogenraad CC, Milstein AD, Ethell IM, Henkemeyer M, Sheng M. GRIP1 controls dendrite morphogenesis by regulating EphB receptor trafficking. Nat Neurosci. 2005;8:906–915. doi: 10.1038/nn1487.10.1038/nn148715965473Geiger JC, Lipka J, Segura I, Hoyer S, Schlager MA, Wulf PS, Weinges S, Demmers J, Hoogenraad CC, Acker-Palmer A. The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development. Dev Cell. 2014;28:381–393. doi: 10.1016/j.devcel.2014.01.018.10.1016/j.devcel.2014.01.01824576423Heisler FF, Lee HK, Gromova KV, Pechmann Y, Schurek B, Ruschkies L, Schroeder M, Schweizer M, Kneussel M. GRIP1 interlinks N-cadherin and AMPA receptors at vesicles to promote combined cargo transport into dendrites. Proc Natl Acad Sci. 2014;111:5030–5035. doi: 10.1073/pnas.1304301111.10.1073/pnas.1304301111PMC397729624639525Lv K, Chen L, Li Y, Li Z, Zheng P, Liu Y, Chen J, Teng J. Trip6 promotes dendritic morphogenesis through dephosphorylated GRIP1-dependent myosin VI and F-actin organization. J Neurosci. 2015;35:2559–2571. doi: 10.1523/JNEUROSCI.2125-14.2015.10.1523/JNEUROSCI.2125-14.2015PMC660562025673849Osten P, Khatri L, Perez JL, Köhr G, Giese G, Daly C, Schulz TW, Wensky A, Lee LM, Ziff EB. Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor. Neuron. 2000;27:313–325. doi: 10.1016/S0896-6273(00)00039-8.10.1016/S0896-6273(00)00039-810985351Chung HJ, Xia J, Scannevin RH, Zhang X, Huganir RL. Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci. 2000;20:7258–7267. doi: 10.1523/JNEUROSCI.20-19-07258.2000.10.1523/JNEUROSCI.20-19-07258.2000PMC677278911007883Chung HJ, Steinberg JP, Huganir RL, Linden DJ. Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression. Science. 2003;300:1751–1755. doi: 10.1126/science.1082915.10.1126/science.108291512805550Kim CH, Chung HJ, Lee HK, Huganir RL. Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression. Proc Natl Acad Sci USA. 2001;98:11725–11730. doi: 10.1073/pnas.211132798.10.1073/pnas.211132798PMC5879711573007Matsuda S, Launey T, Mikawa S, Hirai H. Disruption of AMPA receptor GluR2 clusters following long-term depression induction in cerebellar Purkinje neurons. EMBO J. 2000;19:2765–2774. doi: 10.1093/emboj/19.12.2765.10.1093/emboj/19.12.2765PMC20334910856222Xia J, Chung HJ, Wihler C, Huganir RL, Linden DJ. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Interactions. 2000;28:499–510.11144359Seidenman KJ, Steinberg JP, Huganir R, Malinow R. Glutamate receptor subunit 2 Serine 880 phosphorylation modulates synaptic transmission and mediates plasticity in CA1 pyramidal cells. J Neurosci. 2003;23:9220–9228. doi: 10.1523/JNEUROSCI.23-27-09220.2003.10.1523/JNEUROSCI.23-27-09220.2003PMC674083814534256Gainey MA, Tatavarty V, Nahmani M, Lin H, Turrigiano GG. Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade. Proc Natl Acad Sci. 2015;112:E3590–E3599. doi: 10.1073/pnas.1510754112.10.1073/pnas.1510754112PMC450021026109571Tan HL, Queenan BN, Huganir RL. GRIP1 is required for homeostatic regulation of AMPAR trafficking. Proc Natl Acad Sci. 2015;112:10026–10031. doi: 10.1073/pnas.1512786112.10.1073/pnas.1512786112PMC453861226216979Braithwaite SP, Xia H, Malenka RC. Differential roles for NSF and GRIP/ABP in AMPA receptor cycling. Proc Natl Acad Sci. 2002;99:7096–7101. doi: 10.1073/pnas.102156099.10.1073/pnas.102156099PMC12453412011465DeSouza S, Fu J, States B, Ziff EB. Differential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters. J Neurosci. 2002;22:3493–3503. doi: 10.1523/JNEUROSCI.22-09-03493.2002.10.1523/JNEUROSCI.22-09-03493.2002PMC675837811978826Hirbec H, Francis JC, Lauri SE, Braithwaite SP, Coussen F, Mulle C, Dev KK, Couthino V, Meyer G, Isaac JTR, Collingridge GL, Henley JM. Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP. Neuron. 2003;37:625–638. doi: 10.1016/S0896-6273(02)01191-1.10.1016/S0896-6273(02)01191-1PMC331450212597860Matsuda S, Mikawa S, Hirai H. Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C terminus from binding with glutamate receptor-interacting protein. J Neurochem. 1999;73:1765–1768. doi: 10.1046/j.1471-4159.1999.731765.x.10.1046/j.1471-4159.1999.731765.x10501226Mejias R, Adamczyk A, Anggono V, Niranjan T, Thomas GM, Sharma K. Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism. Proc Natl Acad Sci. 2011;108:4920–4925. doi: 10.1073/pnas.1102233108.10.1073/pnas.1102233108PMC306436221383172Han M, Mejias R, Chiu SL, Rose R, Adamczyk A, Huganir R, Wang T. Mice lacking GRIP1/2 show increased social interactions and enhanced phosphorylation at GluA2-S880. Behav Brain Res. 2017;321:176–184. doi: 10.1016/j.bbr.2016.12.042.10.1016/j.bbr.2016.12.042PMC562802328063882Daw MI, Chittajallu R, Bortolotto ZA, Dev KK, Duprat F, Henley JM, Collingridge GL, Isaac JTR. PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses. Neuron. 2000;28:873–886. doi: 10.1016/S0896-6273(00)00160-4.10.1016/S0896-6273(00)00160-411163273Fu J, DeSouza S, Ziff EB. Intracellular membrane targeting and suppression of Ser880 phosphorylation of glutamate receptor 2 by the linker I-set II domain of AMPA receptor-binding protein. J Neurosci. 2003;23:7592–7601. doi: 10.1523/JNEUROSCI.23-20-07592.2003.10.1523/JNEUROSCI.23-20-07592.2003PMC674074512930798Takamiya K, Mao L, Huganir RL, Linden DJ. The glutamate receptor-interacting protein family of GluR2-binding proteins is required for long-term synaptic depression expression in cerebellar Purkinje cells. J Neurosci. 2008;28:5752–5755. doi: 10.1523/JNEUROSCI.0654-08.2008.10.1523/JNEUROSCI.0654-08.2008PMC258708318509036Mao L, Takamiya K, Thomas G, Lin D, Huganir RL. GRIP1 and 2 regulate activity-dependent AMPA receptor recycling via exocyst complex interactions. Proc Natl Acad Sci. 2010;2010:1–6.PMC297385420956289Lu W, Ziff EB. PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron. 2005;47:407–421. doi: 10.1016/j.neuron.2005.07.006.10.1016/j.neuron.2005.07.00616055064Hayashi T, Huganir RL. Tyrosine phosphorylation and regulation of the AMPA receptor by Src family tyrosine kinases. J Neurosci. 2004;24:6152–6160. doi: 10.1523/JNEUROSCI.0799-04.2004.10.1523/JNEUROSCI.0799-04.2004PMC672965815240807States BA, Khatri L, Ziff EB. Stable synaptic retention of serine-880-phosphorylated GluR2 in hippocampal neurons. Mol Cell Neurosci. 2008;38:189–202. doi: 10.1016/j.mcn.2008.02.003.10.1016/j.mcn.2008.02.003PMC265362318417360Casimiro T, Sossa KG, Uzunova G, Beattie JB, Kurt C, Carroll RC. mGluR and NMDAR activation internalize distinct populations of AMPARs. Mol Cell Neurosci. 2011;48(2):161–170. doi: 10.1016/j.mcn.2011.07.007.10.1016/j.mcn.2011.07.007PMC316374421807099Yamazaki M, Fukaya M, Abe M, Ikeno K, Kakizaki T, Watanabe M, Sakimura K. Differential palmitoylation of two mouse glutamate receptor interacting protein 1 forms with different N-terminal sequences. Neurosci Lett. 2001;304:81–84. doi: 10.1016/S0304-3940(01)01766-9.10.1016/S0304-3940(01)01766-911335060Charych EI, Yu W, Li R, Serwanski DR, Miralles CP, Li X, Yang BY, Pinal N, Walikonis R, De Blas AL. A four PDZ domain-containing splice variant form of GRIP1 is localized in GABAergic and glutamatergic synapses in the brain. J Biol Chem. 2004;279:38978–38990. doi: 10.1074/jbc.M405786200.10.1074/jbc.M40578620015226318Charych EI, Li R, Serwanski DR, Li X, Miralles CP, Pinal N, De Blas AL. Identification and characterization of two novel splice forms of GRIP1 in the rat brain. J Neurochem. 2006;97:884–898. doi: 10.1111/j.1471-4159.2006.03795.x.10.1111/j.1471-4159.2006.03795.x16539648Hanley LJ, Henley JM. Differential roles of GRIP1a and GRIP1b in AMPA receptor trafficking. Neurosci Lett. 2010;485:167–172. doi: 10.1016/j.neulet.2010.09.003.10.1016/j.neulet.2010.09.003PMC331015620837103Thomas GM, Hayashi T, Chiu SL, Chen CM, Huganir RL. Palmitoylation by DHHC5/8 targets GRIP1 to dendritic endosomes to regulate AMPA-R trafficking. Neuron. 2012;73:482–496. doi: 10.1016/j.neuron.2011.11.021.10.1016/j.neuron.2011.11.021PMC334550522325201Misra C, Restituito S, Ferreira J, Rameau GA, Fu J, Ziff EB. Regulation of synaptic structure and function by palmitoylated AMPA receptor binding protein. Mol Cell Neurosci. 2010;43:341–352. doi: 10.1016/j.mcn.2010.01.001.10.1016/j.mcn.2010.01.001PMC306185320083202Takamiya K, Kostourou V, Adams S, Jadeja S, Chalepakis G, Scambler PJ, Huganir RL, Adams RH. A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1. Nat Genet. 2004;36:172–177. doi: 10.1038/ng1292.10.1038/ng129214730302Hong CJ, Hsueh YP. CASK associates with glutamate receptor interacting protein and signaling molecules. Biochem Biophys Res Commun. 2006;351:771–776. doi: 10.1016/j.bbrc.2006.10.113.10.1016/j.bbrc.2006.10.11317084383Atasoy D, Schoch S, Ho A, Nadasy KA, Liu X, Zhang W, Mukherjee K, Nosyreva ED, Fernandez-Chacon R, Missler M, Kavalali ET, Sudhof TC. Deletion of CASK in mice is lethal and impairs synaptic function. Proc Natl Acad Sci. 2007;104:2525–2530. doi: 10.1073/pnas.0611003104.10.1073/pnas.0611003104PMC189297017287346Steiner P, Floyd Sarria JC, Glauser L, Magnin S, Catsicas S, Hirling H. Modulation of receptor cycling by neuron-enriched endosomal protein of 21 kD. J Cell Biol. 2002;157:1197–1209. doi: 10.1083/jcb.200202022.10.1083/jcb.200202022PMC217354112070131Steiner P, Alberi S, Kulangara K, Yersin A, Sarria JCF, Regulier E, Kasas S, Dietler G, Muller D, Catsicas S, Hirling H. Interactions between NEEP21, GRIP1 and GluR2 regulate sorting and recycling of the glutamate receptor subunit GluR2. EMBO J. 2005;24:2873–2884. doi: 10.1038/sj.emboj.7600755.10.1038/sj.emboj.7600755PMC118794016037816Utvik JK, Haglerød C, Mylonakou MNI, Holen T, Kropf M, Hirling H, Skare Laake P, Ottersen OP, Haug FMS, Davanger S. Neuronal enriched endosomal protein of 21 kDa colocalizes with glutamate receptor subunit GLUR2/3 at the postsynaptic membrane. Neuroscience. 2009;158:96–104. doi: 10.1016/j.neuroscience.2008.11.030.10.1016/j.neuroscience.2008.11.03019063943Alberi S, Boda B, Steiner P, Nikonenko I, Hirling H, Muller D. The endosomal protein NEEP21 regulates AMPA receptor-mediated synaptic transmission and plasticity in the hippocampus. Mol Cell Neurosci. 2005;29:313–319. doi: 10.1016/j.mcn.2005.03.011.10.1016/j.mcn.2005.03.01115911354Kulangara K, Kropf M, Glauser L, Magnin S, Alberi S, Yersin A, Hirling H. Phosphorylation of glutamate receptor interacting protein 1 regulates surface expression of glutamate receptors. J Biol Chem. 2007;282:2395–2404. doi: 10.1074/jbc.M606471200.10.1074/jbc.M60647120017121843Ye B, Liao D, Zhang X, Zhang P, Dong H, Huganir RL. GRASP-1: a neuronal RasGEF associated with the AMPA receptor/GRIP complex. Neuron. 2000;26:603–617. doi: 10.1016/S0896-6273(00)81198-8.10.1016/S0896-6273(00)81198-810896157Lu J-M, Liu D-D, Li Z-Y, Ling C, Mei Y-A. Neuritin enhances synaptic transmission in medial prefrontal cortex in mice by increasing CaV3.3 surface expression. Cereb Cortex. 2017;27:3842–3855. doi: 10.1093/cercor/bhx082.10.1093/cercor/bhx08228475719Bakshi K, Gennaro S, Chan CY, Kosciuk M, Liu J, Stucky A, Trenkner E, Friedman E, Nagele RG, Wang H-Y. Prenatal cocaine reduces AMPA receptor synaptic expression through hyperphosphorylation of the synaptic anchoring protein GRIP. J Neurosci. 2009;29:6308–6319. doi: 10.1523/JNEUROSCI.5485-08.2009.10.1523/JNEUROSCI.5485-08.2009PMC272773919439608Bakshi K, Kosciuk M, Nagele RG, Friedman E, Wang HY. Prenatal cocaine exposure increases synaptic localization of a neuronal RasGEF, GRASP-1 via hyperphosphorylation of AMPAR anchoring protein, GRIP. PLoS One. 2011;6:e25019. doi: 10.1371/journal.pone.0025019.10.1371/journal.pone.0025019PMC318133221980374Hoogenraad CC, Popa I, Futai K, Sanchez-Martinez E, Wulf PS, Van Vlijmen T, Dortland BR, Oorschot V, Govers R, Monti M, Heck AJR, Sheng M, Klumperman J, Rehmann H, Jaarsma D, Kapitein LC, Van Der Sluijs P. Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization and maturation of recycling endosomes. PLoS Biol. 2010;8:e1000283. doi: 10.1371/journal.pbio.1000283.10.1371/journal.pbio.1000283PMC280820920098723Chiu SL, Diering GH, Ye B, Takamiya K, Chen CM, Jiang Y, Niranjan T, Schwartz CE, Wang T, Huganir RL. GRASP1 regulates synaptic plasticity and learning through endosomal recycling of AMPA receptors. Neuron. 2017;93:1405–1419.e8. doi: 10.1016/j.neuron.2017.02.031.10.1016/j.neuron.2017.02.031PMC538271428285821Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-page C, Streuli M, Weinberg RJ, Sheng M, Hill C, Carolina N. Interaction between GRIP and liprin-α/SYD2 is required for AMPA receptor targeting University of North Carolina at Chapel Hill. Neuron. 2002;34:39–52. doi: 10.1016/S0896-6273(02)00640-2.10.1016/S0896-6273(02)00640-211931740Ko J, Kim S, Valtschanoff JG, Shin H, Lee J-R, Sheng M, Premont RT, Weinberg RJ, Kim E. Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting. J Neurosci. 2003;23:1667–1677. doi: 10.1523/JNEUROSCI.23-05-01667.2003.10.1523/JNEUROSCI.23-05-01667.2003PMC674197512629171Dunah AW, Hueske E, Wyszynski M, Hoogenraad CC, Jaworski J, Pak DT, Simonetta A, Liu G, Sheng M. LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nat Neurosci. 2005;8:458–467. doi: 10.1038/nn1416.10.1038/nn141615750591Dickinson BA, Jo J, Seok H, Son GH, Whitcomb DJ, Davies CH, Sheng M, Collingridge GL, Cho K. A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin. Mol Brain. 2009;2:1–12. doi: 10.1186/1756-6606-2-18.10.1186/1756-6606-2-18PMC270193419534762Shin H, Wyszynski M, Huh KH, Valtschanoff JG, Lee JR, Ko J, Streuli M, Weinberg RJ, Sheng M, Kim E. Association of the kinesin motor KIF1A with the multimodular protein liprin-α. J Biol Chem. 2003;278:11393–11401. doi: 10.1074/jbc.M211874200.10.1074/jbc.M21187420012522103Davidkova G, Carroll RC. Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus. J Neurosci. 2007;27:13273–13278. doi: 10.1523/JNEUROSCI.3334-07.2007.10.1523/JNEUROSCI.3334-07.2007PMC667340618045921Palenzuela R, Gutiérrez Y, Draffin JE, Lario A, Benoist M, Esteban JA. MAP1B light chain modulates synaptic transmission via AMPA receptor intracellular trapping. J Neurosci. 2017;37:0505–0517. doi: 10.1523/JNEUROSCI.0505-17.2017.10.1523/JNEUROSCI.0505-17.2017PMC659659528904092Zhang J, Wang Y, Chi Z, Keuss M, Pai Y-ME, Kang HC, Shin J, Bugayenko A, Wang H, Xiong Y, Pletnikov MV, Mattson MP, Dawson TM, Dawson VL. The AAA + ATPase, thorase regulates AMPA receptor-dependent synaptic plasticity and behavior. Cell. 2011;22:233–245.PMC308500321496646Umanah GKE, Pignatelli M, Yin X, Chen R, Crawford J, Neifert S, Scarffe L, Behensky AA, Guiberson N, Chang M, Ma E, Kim JW, Castro CC, Mao X, Chen L, Andrabi SA, Pletnikov MV, Pulver AE, Avramopoulos D, Bonci A, Valle D, Dawson TM, Dawson VL. Thorase variants are associated with defects in glutamatergic neurotransmission that can be rescued by Perampanel. Sci Transl Med. 2017;9:eaah4985. doi: 10.1126/scitranslmed.aah4985.10.1126/scitranslmed.aah4985PMC657302529237760Ahrens-Nicklas RC, Umanah GKE, Sondheimer N, Deardorff MA, Wilkens AB, Conlin LK, Santani AB, Nesbitt A, Juulsola J, Ma E, Dawson TM, Dawson VL, Marsh ED. Precision therapy for a new disorder of AMPA receptor recycling due to mutations in ATAD1. Neurol Genet. 2017;3:e130. doi: 10.1212/NXG.0000000000000130.10.1212/NXG.0000000000000130PMC528901728180185Piard J, Umanah GKE, Harms FL, Abalde-Atristain L, Amram D, Chang M, Chen R, Alawi M, Salpietro V, Rees MI, Chung SK, Houlden H, Verloes A, Dawson TM, Dawson VL, Van Maldergem L, Kutsche K. A homozygous ATAD1 mutation impairs postsynaptic AMPA receptor trafficking and causes a lethal encephalopathy. Brain. 2018;141:651–661. doi: 10.1093/brain/awx377.10.1093/brain/awx377PMC583772129390050Torres R, Firestein BL, Dong H, Staudinger J, Olson EN, Huganir RL, Bredt DS, Gale NW, Yancopoulos GD. PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron. 1998;21:1453–1463. doi: 10.1016/S0896-6273(00)80663-7.10.1016/S0896-6273(00)80663-79883737Hruska M, Dalva MB. Ephrin regulation of synapse formation, function and plasticity. Mol Cell Neurosci. 2012;50:35–44. doi: 10.1016/j.mcn.2012.03.004.10.1016/j.mcn.2012.03.004PMC363156722449939Irie F, Okuno M, Pasquale EB, Yamaguchi Y. EphrinB-EphB signalling regulates clathrin-mediated endocytosis through tyrosine phosphorylation of synaptojanin 1. Nat Cell Biol. 2005;7:501–509. doi: 10.1038/ncb1252.10.1038/ncb1252PMC147316715821731Hussain NK, Thomas GM, Luo J, Huganir RL. Regulation of AMPA receptor subunit GluA1 surface expression by PAK3 phosphorylation. Proc Natl Acad Sci. 2015;112:E5883–E5890. doi: 10.1073/pnas.1518382112.10.1073/pnas.1518382112PMC462935326460013Kayser MS, McClelland AC, Hughes EG, Dalva MB. Intracellular and trans-synaptic regulation of glutamatergic synaptogenesis by EphB receptors. J Neurosci. 2006;26:12152–12164. doi: 10.1523/JNEUROSCI.3072-06.2006.10.1523/JNEUROSCI.3072-06.2006PMC667544617122040Fu AKY, Hung KW, Fu WY, Shen C, Chen Y, Xia J, Lai KO, Ip NY. APCCdh1mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity. Nat Neurosci. 2011;14:181–191. doi: 10.1038/nn.2715.10.1038/nn.271521186356Contractor A, Rogers C, Maron C, Heinemann SF. Trans-synaptic Eph receptor-ephrin signaling in hippocampal mossy fiber LTP. Science. 2002;296:1864–1869. doi: 10.1126/science.1069081.10.1126/science.106908112052960Aoto J, Ting P, Maghsoodi B, Xu N, Henkemeyer M, Chen L. Postsynaptic EphrinB3 promotes shaft glutamatergic synapse formation. J Neurosci. 2007;27:7508–7519. doi: 10.1523/JNEUROSCI.0705-07.2007.10.1523/JNEUROSCI.0705-07.2007PMC667260517626212Antion MD, Christie LA, Bond AM, Dalva MB, Contractor A. Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses. Mol Cell Neurosci. 2010;45:378–388. doi: 10.1016/j.mcn.2010.07.011.10.1016/j.mcn.2010.07.011PMC296268320678574Hruska M, Henderson NT, Xia NL, Le Marchand SJ, Dalva MB. Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3. Nat Neurosci. 2015;18:1594–1605. doi: 10.1038/nn.4140.10.1038/nn.4140PMC539645726479588Hering H, Lin C, Sheng M. Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J Neurosci. 2003;23:3262–3271. doi: 10.1523/JNEUROSCI.23-08-03262.2003.10.1523/JNEUROSCI.23-08-03262.2003PMC674229912716933Essmann CL, Martinez E, Geiger JC, Zimmer M, Traut MH, Stein V, Klein R, Acker-Palmer A. Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors. Nat Neurosci. 2008;11:1035–1043. doi: 10.1038/nn.2171.10.1038/nn.217119160501Bouzioukh F, Wilkinson GA, Adelmann G, Frotscher M, Stein V, Klein R. Tyrosine phosphorylation sites in ephrinB2 are required for hippocampal long-term potentiation but not long-term depression. J Neurosci. 2007;27:11279–11288. doi: 10.1523/JNEUROSCI.3393-07.2007.10.1523/JNEUROSCI.3393-07.2007PMC667301517942722Pfennig S, Foss F, Bissen D, Harde E, Treeck JC, Segarra M, Acker-Palmer A. GRIP1 binds to ApoER2 and EphrinB2 to induce activity-dependent AMPA receptor insertion at the synapse. Cell Rep. 2017;21:84–96. doi: 10.1016/j.celrep.2017.09.019.10.1016/j.celrep.2017.09.019PMC564080628978486Qiu S, Zhao LF, Korwek KM, Weeber EJ. Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus. J Neurosci. 2006;26:12943–12955. doi: 10.1523/JNEUROSCI.2561-06.2006.10.1523/JNEUROSCI.2561-06.2006PMC667496417167084Weeber EJ, Beffert U, Jones C, Christian JM, Förster E, David Sweatt J, Herz J. Reelin and apoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J Biol Chem. 2002;277:39944–39952. doi: 10.1074/jbc.M205147200.10.1074/jbc.M20514720012167620Dumanis SB, Cha HJ, Song JM, Trotter JH, Spitzer M, Lee JY, Weeber EJ, Scott Turner R, Pak DTS, William Rebeck G, Hoe HS. ApoE receptor 2 regulates synapse and dendritic spine formation. PLoS One. 2011;6:e17203. doi: 10.1371/journal.pone.0017203.10.1371/journal.pone.0017203PMC303966621347244Staudinger J, Zhou J, Burgess R, Elledge SJ, Olson EN. PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system. J Cell Biol. 1995;128:263–271. doi: 10.1083/jcb.128.3.263.10.1083/jcb.128.3.263PMC21203447844141Iwakura Y, Nagano T, Kawamura M, Horikawa H, Ibaraki K, Takei N, Nawa H. N-methyl-d-aspartate-induced a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor down-regulation involves interaction of the carboxyl terminus of GluR2/3 with Pick1: ligand-binding studies using Sindbis vectors carrying AMPA receptor d. J Biol Chem. 2001;276:40025–40032. doi: 10.1074/jbc.M103125200.10.1074/jbc.M10312520011498531Perez JL, Khatri L, Chang C, Srivastava S, Osten P, Ziff EB. PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. J Neurosci. 2001;21:5417–5428. doi: 10.1523/JNEUROSCI.21-15-05417.2001.10.1523/JNEUROSCI.21-15-05417.2001PMC676265811466413Hanley JG, Henley JM. PICK1 is a calcium-sensor for NMDA-induced AMPA receptor trafficking. EMBO J. 2005;24:3266–3278. doi: 10.1038/sj.emboj.7600801.10.1038/sj.emboj.7600801PMC122469116138078Jin W, Ge W-P, Xu J, Cao M, Peng L, Yung W, Liao D, Duan S, Zhang M, Xia J. Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity. J Neurosci. 2006;26:2380–2390. doi: 10.1523/JNEUROSCI.3503-05.2006.10.1523/JNEUROSCI.3503-05.2006PMC679365216510715Ho MT-W, Pelkey KA, Topolnik L, Petralia RS, Takamiya K, Xia J, Huganir RL, Lacaille J-C, McBain CJ. Developmental expression of Ca2+-permeable AMPA receptors underlies depolarization-induced long-term depression at mossy fiber CA3 pyramid synapses. J Neurosci. 2007;27:11651–11662. doi: 10.1523/JNEUROSCI.2671-07.2007.10.1523/JNEUROSCI.2671-07.2007PMC667323917959808Terashima A, Pelkey KA, Rah JC, Suh YH, Roche KW, Collingridge GLL, McBain CJ, Isaac JTR. An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity. Neuron. 2008;57:872–882. doi: 10.1016/j.neuron.2008.01.028.10.1016/j.neuron.2008.01.028PMC233689518367088Steinberg JP, Takamiya K, Shen Y, Xia J, Rubio ME, Yu S, Jin W, Thomas GM, Linden DJ, Huganir RL. Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron. 2006;49:845–860. doi: 10.1016/j.neuron.2006.02.025.10.1016/j.neuron.2006.02.02516543133Jo J, Heon S, Kim MJ, Son GH, Park Y, Jeremy M, Weiss JL, Sheng M, Collingridge GL. Metabotropic glutamate receptor-mediated LTD involves two interacting Ca2+ sensors, NCS-1 and PICK1. Neuron. 2008;60:1095–1111. doi: 10.1016/j.neuron.2008.10.050.10.1016/j.neuron.2008.10.050PMC331090519109914Bellone C, Lüscher C. Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression. Nat Neurosci. 2006;9:636–641. doi: 10.1038/nn1682.10.1038/nn168216582902Lin D-T, Huganir RL. PICK1 and phosphorylation of the glutamate receptor 2 (GluR2) AMPA receptor subunit regulates GluR2 recycling after NMDA receptor-induced internalization. J Neurosci. 2007;27:13903–13908. doi: 10.1523/JNEUROSCI.1750-07.2007.10.1523/JNEUROSCI.1750-07.2007PMC667362418077702Sossa KG, Beattie JB, Carroll RC. AMPAR exocytosis through NO modulation of PICK1. Neuropharmacology. 2007;53:92–100. doi: 10.1016/j.neuropharm.2007.04.005.10.1016/j.neuropharm.2007.04.005PMC204030317555774Citri A, Bhattacharyya S, Ma C, Morishita W, Fang S, Rizo J, Malenka RC. Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression. J Neurosci. 2010;30:16437–16452. doi: 10.1523/JNEUROSCI.4478-10.2010.10.1523/JNEUROSCI.4478-10.2010PMC300447721147983Terashima A, Cotton L, Dev KK, Meyer G, Zaman S, Duprat F, Henley JM, Collingridge GL, Isaac JT. Regulation of synaptic strength and AMPA receptor subunit composition by PICK1. J Neurosci. 2004;24:5381–5390. doi: 10.1523/JNEUROSCI.4378-03.2004.10.1523/JNEUROSCI.4378-03.2004PMC331090715190111Gardner SM, Takamiya K, Xia J, Suh JG, Johnson R, Yu S, Huganir RL. Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron. 2005;45:903–915. doi: 10.1016/j.neuron.2005.02.026.10.1016/j.neuron.2005.02.02615797551Sossa KG, Court BL, Carroll RC. NMDA receptors mediate calcium-dependent, bidirectional changes in dendritic PICK1 clustering. Mol Cell Neurosci. 2006;31:574–585. doi: 10.1016/j.mcn.2005.11.011.10.1016/j.mcn.2005.11.01116406232Volk L, Kim C-H, Takamiya K, Yu Y, Huganir RL. Developmental regulation of protein interacting with C kinase 1 (PICK1) function in hippocampal synaptic plasticity and learning. Proc Natl Acad Sci. 2010;107:21784–21789. doi: 10.1073/pnas.1016103107.10.1073/pnas.1016103107PMC300302821106762Makuch L, Volk L, Anggono V, Johnson RC, Yu Y, Duning K, Kremerskothen J, Xia J, Takamiya K, Huganir RL. Regulation of AMPA receptor function by the human memory-associated gene KIBRA. Neuron. 2011;71:1022–1029. doi: 10.1016/j.neuron.2011.08.017.10.1016/j.neuron.2011.08.017PMC320057521943600Anggono V, Clem RL, Huganir R. PICK1 loss of function occludes homeostatic synaptic scaling. J Neurosci. 2011;31:2188–2196. doi: 10.1523/JNEUROSCI.5633-10.2011.10.1523/JNEUROSCI.5633-10.2011PMC307103921307255Shao X, Zhu L, Wang Y, Lu Y, Wang W, Zhu J, Shen Y, Xia J, Luo J. Threonine 82 at the PDZ domain of PICK1 is critical for AMPA receptor interaction and localization. Neurochem Int. 2010;56:962–970. doi: 10.1016/j.neuint.2010.04.006.10.1016/j.neuint.2010.04.00620403402Yagishita S, Murayama M, Ebihara T, Maruyama K, Takashima A. Glycogen synthase kinase 3β-mediated phosphorylation in the most C-terminal region of protein interacting with C kinase 1 (PICK1) regulates the binding of PICK1 to glutamate receptor subunit GluA2. J Biol Chem. 2015;290:29438–29448. doi: 10.1074/jbc.M114.619668.10.1074/jbc.M114.619668PMC470594626472923Thomas GM, Hayashi T, Huganir RL, Linden DJ. DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression. J Neurosci. 2013;33:15401–15407. doi: 10.1523/JNEUROSCI.1283-13.2013.10.1523/JNEUROSCI.1283-13.2013PMC378262024068808Joch M, Ase AR, Chen CX-Q, MacDonald PA, Kontogiannea M, Corera AT, Brice A, Séguéla P, Fon EA. Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Mol Biol Cell. 2007;18:3105–3118. doi: 10.1091/mbc.e05-11-1027.10.1091/mbc.e05-11-1027PMC194938517553932Lu W, Khatri L, Ziff EB. Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptor subunit GluA2 from the endoplasmic reticulum is stimulated by a complex containing Ca2+/calmodulin-activated kinase II (CaMKII) and PICK1 protein and by release of Ca2+ from internal stores. J Biol Chem. 2014;289:19218–19230. doi: 10.1074/jbc.M113.511246.10.1074/jbc.M113.511246PMC408195624831007Hanley JG, Khatri L, Hanson PI, Ziff EB. NSF ATPase and α-/β-SNAPs disassemble the AMPA receptor-PICK1 complex. Neuron. 2002;34:53–67. doi: 10.1016/S0896-6273(02)00638-4.10.1016/S0896-6273(02)00638-411931741Hanley JG. NSF binds calcium to regulate its interaction with AMPA receptor subunit GluR2. J Neurochem. 2007;101:1644–1650. doi: 10.1111/j.1471-4159.2007.04455.x.10.1111/j.1471-4159.2007.04455.xPMC197625017302911Rocca DL, Martin S, Jenkins EL, Hanley JG. Inhibition of Arp2/3-mediated actin polymerisation by PICK1 regulates neuronal morphology and AMPA receptor endocytosis. Cell. 2008;10:259–271.PMC266461318297063Nakamura Y, Wood CL, Patton AP, Jaafari N, Henley JM, Mellor JR, Hanley JG. PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity. EMBO J. 2011;30:719–730. doi: 10.1038/emboj.2010.357.10.1038/emboj.2010.357PMC304195321252856Rocca DL, Amici M, Antoniou A, Suarez EB, Halemani N, Murk K, McGarvey J, Jaafari N, Mellor JR, Collingridge GL, Hanley JG. The Small GTPase Arf1 Modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity. Neuron. 2013;79:293–307. doi: 10.1016/j.neuron.2013.05.003.10.1016/j.neuron.2013.05.003PMC372541623889934Rocca DL, Hanley JG. PICK1 links AMPA receptor stimulation to Cdc42. Neurosci Lett. 2015;585:155–159. doi: 10.1016/j.neulet.2014.11.046.10.1016/j.neulet.2014.11.046PMC430040225475687Madasu Y, Yang C, Boczkowska M, Bethoney KA, Zwolak A, Rebowski G, Svitkina T, Dominguez R. PICK1 is implicated in organelle motility in an Arp2/3 complex-independent manner. Mol Biol Cell. 2015;26:1308–1322. doi: 10.1091/mbc.E14-10-1448.10.1091/mbc.E14-10-1448PMC445417825657323Xu J, Wang N, Luo JH, Xia J. Syntabulin regulates the trafficking of PICK1-containing vesicles in neurons. Sci Rep. 2016;6:1–15. doi: 10.1038/s41598-016-0001-8.10.1038/s41598-016-0001-8PMC475143026868290Haglerød C, Kapic A, Boulland JL, Hussain S, Holen T, Skare Laake P, Ottersen OP, Haug FMS, Davanger S. Protein interacting with C kinase 1 (PICK1) and GluR2 are associated with presynaptic plasma membrane and vesicles in hippocampal excitatory synapses. Neuroscience. 2009;158:242–252. doi: 10.1016/j.neuroscience.2008.11.029.10.1016/j.neuroscience.2008.11.02919071197Haglerød C, Hussain S, Nakamura Y, Xia J, Haug FMS, Ottersen OP, Henley JM, Davanger S. Presynaptic PICK1 facilitates trafficking of AMPA-receptors between active zone and synaptic vesicle pool. Neuroscience. 2017;344:102–112. doi: 10.1016/j.neuroscience.2016.12.042.10.1016/j.neuroscience.2016.12.04228057533Fiuza M, Rostosky CM, Parkinson GT, Bygrave AM, Halemani N, Baptista M, Milosevic I, Hanley JG. PICK1 regulates AMP receptor endocytosis via direct interaction with AP2 α-appendage and dynamin. Rockefeller Univ Press J Cell Biol. 2017;216:3323–3338. doi: 10.1083/jcb.201701034.10.1083/jcb.201701034PMC562654128855251Cao M, Xu J, Shen C, Kam C, Huganir RL, Xia J. PICK1 ICA69 heteromeric BAR domain complex regulates synaptic targeting and surface expression of AMPA receptors. J Neurosci. 2007;27:12945–12956. doi: 10.1523/JNEUROSCI.2040-07.2007.10.1523/JNEUROSCI.2040-07.2007PMC667328818032668Wang Z, Wang YN, Sun CL, Yang D, Da SuL, Xie YJ, Zhou L, Wang Y, Shen Y. C-terminal domain of ICA69 interacts with PICK1 and acts on trafficking of PICK1–PKCα complex and cerebellar plasticity. PLoS One. 2013;8:1–17. doi: 10.1371/annotation/5fa9cfb4-9964-4586-845d-d8205f318d68.10.1371/annotation/5fa9cfb4-9964-4586-845d-d8205f318d68PMC386525324358315Xu J, Kam C, Luo J, Xia J. PICK1 mediates synaptic recruitment of AMPA receptors at neurexin-induced postsynaptic sites. J Neurosci. 2014;34:15415–15424. doi: 10.1523/JNEUROSCI.0296-14.2014.10.1523/JNEUROSCI.0296-14.2014PMC660844825392508Anggono V, Koç-Schmitz Y, Widagdo J, Kormann J, Quan A, Chen C-M, Robinson PJ, Choi S-Y, Linden DJ, Plomann M, Huganir RL. PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression. Proc Natl Acad Sci. 2013;110:13976–13981. doi: 10.1073/pnas.1312467110.10.1073/pnas.1312467110PMC375226123918399Widagdo J, Fang H, Jang SE, Anggono V. PACSIN1 regulates the dynamics of AMPA receptor trafficking. Sci Rep. 2016;6:1–9. doi: 10.1038/srep31070.10.1038/srep31070PMC497326027488904Breiderhoff T, Christiansen GB, Pallesen LT, Vaegter C, Nykjaer A, Holm MM, Glerup S, Willnow TE. Sortilin-related receptor SORCS3 is a postsynaptic modulator of synaptic depression and fear extinction. PLoS One. 2013;8:1–15. doi: 10.1371/journal.pone.0075006.10.1371/journal.pone.0075006PMC377787824069373Christiansen GB, Andersen KH, Riis S, Nykjaer A, Bolcho U, Jensen MS, Holm MM. The sorting receptor SorCS3 is a stronger regulator of glutamate receptor functions compared to GABAergic mechanisms in the hippocampus. Hippocampus. 2017;27:235–248. doi: 10.1002/hipo.22689.10.1002/hipo.2268927935149Bassani S, Cingolani LA, Valnegri P, Folci A, Zapata J, Gianfelice A, Sala C, Goda Y, Passafaro M. The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking. Neuron. 2012;73:1143–1158. doi: 10.1016/j.neuron.2012.01.021.10.1016/j.neuron.2012.01.021PMC331499722445342Madsen KL, Eriksen J, Milan-Lobo L, Han DS, Niv MY, Ammendrup-Johnsen I, Henriksen U, Bhatia VK, Stamou D, Sitte HH, McMahon HT, Weinstein H, Gether U. Membrane localization is critical for activation of the PICK1 BAR domain. Traffic. 2008;9:1327–1343. doi: 10.1111/j.1600-0854.2008.00761.x.10.1111/j.1600-0854.2008.00761.xPMC362272618466293Karlsen ML, Thorsen TS, Johner N, Ammendrup-johnsen I, Erlendsson S, Tian X, Simonsen JB, Høiberg-nielsen R, Christensen NM, Khelashvili G, Streicher W, Teilum K, Vestergaard B, Weinstein H, Gether U, Arleth L, Madsen KL. Structure of dimeric and tetrameric complexes of the BAR domain protein PICK1 determined by small-angle X-ray scattering. Structure. 2015;23:1258–1270. doi: 10.1016/j.str.2015.04.020.10.1016/j.str.2015.04.020PMC450231426073603Erlendsson S, Arleth L, Madsen KL. Response to the challenges of polydisperse SAXS data analysis: two different SAXS studies of PICK1 produce different structural models. Structure. 2015;23:1669–1670. doi: 10.1016/j.str.2015.10.008.10.1016/j.str.2015.10.00826536377Boczkowska M, Rebowski G, Dominguez R. The challenges of polydisperse SAXS data analysis: two SAXS studies of PICK1 produce different structural models. Structure. 2015;23:1967–1968. doi: 10.1016/j.str.2015.10.007.10.1016/j.str.2015.10.007PMC498499826536376Zhu J, Shang Y, Zhang M. Mechanistic basis of MAGUK-organized complexes in synaptic development and signalling. Nat Rev Neurosci. 2016;17:209–223. doi: 10.1038/nrn.2016.18.10.1038/nrn.2016.1826988743Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW. SAP97 is associated with the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit. J Biol Chem. 1998;273:19518–19524. doi: 10.1074/jbc.273.31.19518.10.1074/jbc.273.31.195189677374Fukata Y, Tzingounis AV, Trinidad JC, Fukata M, Burlingame AL, Nicoll RA, Bredt DS. Molecular constituents of neuronal AMPA receptors. J Cell Biol. 2005;169:399–404. doi: 10.1083/jcb.200501121.10.1083/jcb.200501121PMC217193615883194Cai C, Coleman SK, Niemi K, Keinänen K. Selective binding of synapse-associated protein 97 to GluR-A α-amino-5-hydroxy-3-methyl-4-isoxazole propionate receptor subunit is determined by a novel sequence motif. J Biol Chem. 2002;277:31484–31490. doi: 10.1074/jbc.M204354200.10.1074/jbc.M20435420012070168Cho KO, Hunt CA, Kennedy MB. The rat brain postsynaptic density fraction contains a homolog of the drosophila discs-large tumor suppressor protein. Neuron. 1992;9:929–942. doi: 10.1016/0896-6273(92)90245-9.10.1016/0896-6273(92)90245-91419001Kistner U, Wenzel BM, Veh RW, Cases-Langhoff C, Garner AM, Appeltauer U, Voss B, Gundelfinger ED, Garner CC. SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A. J Biol Chem. 1993;268:4580–4583.7680343Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RGM, Morrison JH, O’Dell TJ, Grant SGN. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature. 1998;396:433–439. doi: 10.1038/24790.10.1038/247909853749Nagura H, Ishikawa Y, Kobayashi K, Takao K, Tanaka T, Nishikawa K, Tamura H, Shiosaka S, Suzuki H, Miyakawa T, Fujiyoshi Y, Doi T. Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice. Mol Brain. 2012;5:1. doi: 10.1186/1756-6606-5-43.10.1186/1756-6606-5-43PMC357536723268962El-Husseini A, Schnell E, Chetkovich D. PSD-95 involvement in maturation of excitatory synapses. Science. 2000;290:1364–1368.11082065Ehrlich I, Klein M, Rumpel S, Malinow R. PSD-95 is required for activity-driven synapse stabilization. Proc Natl Acad Sci. 2007;104:4176–4181. doi: 10.1073/pnas.0609307104.10.1073/pnas.0609307104PMC182072817360496Béïque J-C, Andrade R. PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex. J Physiol. 2003;546:859–867. doi: 10.1113/jphysiol.2002.031369.10.1113/jphysiol.2002.031369PMC234259912563010Stein V, House DRC, Bredt DS, Nicoll RA. Postsynaptic density-95 mimics and occludes hippocampal long-term potentiation and enhances long-term depression. J Neurosci. 2003;23:5503–5506. doi: 10.1523/JNEUROSCI.23-13-05503.2003.10.1523/JNEUROSCI.23-13-05503.2003PMC674124612843250Ehrlich I, Malinow R. Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci. 2004;24:916–927. doi: 10.1523/JNEUROSCI.4733-03.2004.10.1523/JNEUROSCI.4733-03.2004PMC672981614749436Elias GM, Funke L, Stein V, Grant SG, Bredt DS, Nicoll RA. Synapse-specific and developmentally regulated targeting of AMPA receptors by a family of MAGUK scaffolding proteins. Neuron. 2006;52:307–320. doi: 10.1016/j.neuron.2006.09.012.10.1016/j.neuron.2006.09.01217046693Beique J-C, Lin D-T, Kang M-G, Aizawa H, Takamiya K, Huganir RL. Synapse-specific regulation of AMPA receptor function by PSD-95. Proc Natl Acad Sci. 2006;103:19535–19540. doi: 10.1073/pnas.0608492103.10.1073/pnas.0608492103PMC174826017148601Carlisle HJ, Fink AE, Grant SGN, O’dell TJ. Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity. J Physiol. 2008;586:5885–5900. doi: 10.1113/jphysiol.2008.163469.10.1113/jphysiol.2008.163469PMC265541618936077Zhao J, Murata Y, Constantine-paton M. Eye opening and PSD95 are required for long-term potentiation in developing superior colliculus. Proc Natl Acad Sci. 2013;110:707–712. doi: 10.1073/pnas.1215854110.10.1073/pnas.1215854110PMC354577023267080Xu W, Schlüter OM, Steiner P, Czervionke BL, Sabatini BL, Malenka RC. Molecular dissociation of the role of PSD-95 in regulating synaptic strength and LTD. Neuron. 2008;57:248–262. doi: 10.1016/j.neuron.2007.11.027.10.1016/j.neuron.2007.11.027PMC314718018215622Yudowski GA, Olsen O, Adesnik H, Marek KW, Bredt DS. Acute inactivation of PSD-95 destabilizes AMPA receptors at hippocampal synapses. PLoS One. 2013;8:1–9. doi: 10.1371/journal.pone.0053965.10.1371/journal.pone.0053965PMC354696423342049MacGillavry HD, Song Y, Raghavachari S, Blanpied TA. Nanoscale scaffolding domains within the postsynaptic density concentrate synaptic ampa receptors. Neuron. 2013;78:615–622. doi: 10.1016/j.neuron.2013.03.009.10.1016/j.neuron.2013.03.009PMC366835223719161Nair D, Hosy E, Petersen JD, Constals A, Giannone G, Choquet D, Sibarita J-B. Super-resolution imaging reveals that AMPA receptors inside synapses are dynamically organized in nanodomains regulated by PSD95. J Neurosci. 2013;33:13204–13224. doi: 10.1523/JNEUROSCI.2381-12.2013.10.1523/JNEUROSCI.2381-12.2013PMC661972023926273Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt DS, Nicoll RA. Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature. 2000;408:936–943. doi: 10.1038/35050030.10.1038/3505003011140673Bats C, Groc L, Choquet D. The interaction between stargazin and PSD-95 regulates AMPA receptor surface trafficking. Neuron. 2007;53:719–734. doi: 10.1016/j.neuron.2007.01.030.10.1016/j.neuron.2007.01.03017329211Sainlos M, Tigaret C, Poujol C, Olivier NB, Bard L, Breillat C, Thiolon K, Choquet D, Imperiali B. Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization. Nat Chem Biol. 2011;7:81–91. doi: 10.1038/nchembio.498.10.1038/nchembio.49821186349Opazo P, Sainlos M, Choquet D. Regulation of AMPA receptor surface diffusion by PSD-95 slots. Curr Opin Neurobiol. 2012;22:453–460. doi: 10.1016/j.conb.2011.10.010.10.1016/j.conb.2011.10.01022051694Dakoji S, Tomita S, Karimzadegan S, Nicoll RA, Bredt DS. Interaction of transmembrane AMPA receptor regulatory proteins with multiple membrane associated guanylate kinases. Neuropharmacology. 2003;45:849–856. doi: 10.1016/S0028-3908(03)00267-3.10.1016/S0028-3908(03)00267-314529722Penn AC, Zhang CL, Georges F, Royer L, Breillat C, Hosy E, Petersen JD, Humeau Y, Choquet D. Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors. Nature. 2017;549:384–388. doi: 10.1038/nature23658.10.1038/nature23658PMC568335328902836Mondin M, Labrousse V, Hosy E, Heine M, Tessier B, Levet F, Poujol C, Blanchet C, Choquet D, Thoumine O. Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds. J Neurosci. 2011;31:13500–13515. doi: 10.1523/JNEUROSCI.6439-10.2011.10.1523/JNEUROSCI.6439-10.2011PMC662329121940442Jang S, Oh D, Lee Y, Hosy E, Shin H, Van Riesen C, Whitcomb D, Warburton JM, Jo J, Kim D, Kim SG, Um SM, Kwon SK, Kim MH, Roh JD, Woo J, Jun H, Lee D, Mah W, Kim H, Kaang BK, Cho K, Rhee JS, Choquet D, Kim E. Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity. Nat Neurosci. 2015;19:84–93. doi: 10.1038/nn.4176.10.1038/nn.4176PMC501077826595655Matt L, Kim K, Hergarden AC, Patriarchi T, Malik ZA, Park DK, Chowdhury D, Buonarati OR, Henderson PB, Gökçek Saraç Ç, Zhang Y, Mohapatra D, Horne MC, Ames JB, Hell JW. α-Actinin anchors PSD-95 at postsynaptic sites. Neuron. 2018;97:1094–1109. doi: 10.1016/j.neuron.2018.01.036.10.1016/j.neuron.2018.01.036PMC596373429429936Schlüter OM, Xu W, Malenka RC. Alternative N-terminal domains of PSD-95 and SAP97 govern activity-dependent regulation of synaptic AMPA receptor function. Neuron. 2006;51:99–111. doi: 10.1016/j.neuron.2006.05.016.10.1016/j.neuron.2006.05.01616815335Zhang P, Lisman JE. Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons. J Neurophysiol. 2012;107:1058–1066. doi: 10.1152/jn.00526.2011.10.1152/jn.00526.2011PMC328945222114157El-Husseini AE, Craven SE, Chetkovich DM, Firestein BL, Schnell E, Aoki C, Bredt DS. Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering. J Cell Biol. 2000;148:159–171. doi: 10.1083/jcb.148.1.159.10.1083/jcb.148.1.159PMC215621310629226El-Husseini AED, Schnell E, Dakoji S, Sweeney N, Zhou Q, Prange O, Gauthier-Campbell C, Aguilera-Moreno A, Nicoll RA, Bredt DS. Synaptic strength regulated by palmitate cycling on PSD-95. Cell. 2002;108:849–863. doi: 10.1016/S0092-8674(02)00683-9.10.1016/S0092-8674(02)00683-911955437Jeyifous O, Lin EI, Chen X, Antinone SE, Mastro R, Drisdel R, Reese TS, Green WN. Palmitoylation regulates glutamate receptor distributions in postsynaptic densities through control of PSD95 conformation and orientation. Proc Natl Acad Sci. 2016;113:E8482–E8491. doi: 10.1073/pnas.1612963113.10.1073/pnas.1612963113PMC520654727956638Fukata M, Fukata Y, Adesnik H, Nicoll RA, Bredt DS. Identification of PSD-95 palmitoylating enzymes. Neuron. 2004;44:987–996. doi: 10.1016/j.neuron.2004.12.005.10.1016/j.neuron.2004.12.00515603741Yokoi N, Fukata Y, Sekiya A, Murakami T, Kobayashi K, Fukata M. Identification of PSD-95 depalmitoylating enzymes. J Neurosci. 2016;36:6431–6444. doi: 10.1523/JNEUROSCI.0419-16.2016.10.1523/JNEUROSCI.0419-16.2016PMC501578027307232Sturgill JF, Steiner P, Czervionke BL, Sabatini BL. Distinct domains within PSD-95 mediate synaptic incorporation, stabilization, and activity-dependent trafficking. J Neurosci. 2009;29:12845–12854. doi: 10.1523/JNEUROSCI.1841-09.2009.10.1523/JNEUROSCI.1841-09.2009PMC278708919828799Zhang Y, Matt L, Patriarchi T, Malik ZA, Chowdhury D, Park DK, Renieri A, Ames JB, Hell JW. Capping of the N-terminus of PSD-95 by calmodulin triggers its postsynaptic release. EMBO J. 2014;33:1341–1353.PMC419412324705785Noritake J, Fukata Y, Iwanaga T, Hosomi N, Tsutsumi R, Matsuda N, Tani H, Iwanari H, Mochizuki Y, Kodama T, Matsuura Y, Bredt DS, Hamakubo T, Fukata M. Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95. J Cell Biol. 2009;186:147–160. doi: 10.1083/jcb.200903101.10.1083/jcb.200903101PMC271299519596852Chowdhury D, Hell JW. Homeostatic synaptic scaling: molecular regulators of synaptic AMPA-type glutamate receptors. F1000Research. 2018;7:234. doi: 10.12688/f1000research.13561.1.10.12688/f1000research.13561.1PMC583290729560257Steiner P, Higley MJ, Xu W, Czervionke BL, Malenka RC, Sabatini BL. Destabilization of the postsynaptic density by PSD-95 serine 73 phosphorylation inhibits spine growth and synaptic plasticity. Neuron. 2008;60:788–802. doi: 10.1016/j.neuron.2008.10.014.10.1016/j.neuron.2008.10.014PMC267108319081375Kim MJ, Futai K, Jo J, Hayashi Y, Cho K, Sheng M. Synaptic accumulation of PSD-95 and synaptic function regulated by phosphorylation of serine-295 of PSD-95. Neuron. 2007;56:488–502. doi: 10.1016/j.neuron.2007.09.007.10.1016/j.neuron.2007.09.00717988632Nelson CD, Kim MJ, Hsin H, Chen Y, Sheng M. Phosphorylation of threonine-19 of PSD-95 by GSK-3 is required for PSD-95 mobilization and long-term depression. J Neurosci. 2013;33:12122–12135. doi: 10.1523/JNEUROSCI.0131-13.2013.10.1523/JNEUROSCI.0131-13.2013PMC392968723864697Wu Q, Sun M, Bernard LP, Zhang H. Postsynaptic density 95 (PSD-95) serine 561 phosphorylation regulates a conformational switch and bidirectional dendritic spine structural plasticity. J Biol Chem. 2017;292:16150–16160. doi: 10.1074/jbc.M117.782490.10.1074/jbc.M117.782490PMC562504628790172Pedersen SW, Albertsen L, Moran GE, Levesque B, Pedersen SB, Bartels L, Wapenaar H, Ye F, Zhang M, Bowen ME, Strømgaard K. Site-specific phosphorylation of PSD-95 PDZ domains reveals fine-tuned regulation of protein–protein interactions. ACS Chem Biol. 2017;12:2313–2323. doi: 10.1021/acschembio.7b00361.10.1021/acschembio.7b00361PMC608195728692247Colledge M, Snyder EM, Crozier RA, Soderling JA, Jin Y, Langeberg LK, Lu H, Bear MF, Scott JD. Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron. 2003;40:595–607. doi: 10.1016/S0896-6273(03)00687-1.10.1016/S0896-6273(03)00687-1PMC396380814642282Bianchetta MJ, Lam TT, Jones SN, Morabito MA. Cdk5 regulates PSD-95 ubiquitination in neurons. J Neurosci. 2011;31:12029–12035. doi: 10.1523/JNEUROSCI.2388-11.2011.10.1523/JNEUROSCI.2388-11.2011PMC319040121849563Colledge M, Dean RA, Scott GK, Langeberg LK, Huganir RL, Scott JD. Targeting of PKA to glutamate receptors through a MAGUK–AKAP complex. Neuron. 2000;27:107–119. doi: 10.1016/S0896-6273(00)00013-1.10.1016/S0896-6273(00)00013-110939335Bhattacharyya S, Biou V, Xu W, Schlüter OM, Malenka RC. A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. Nat Neurosci. 2009;12:172–181. doi: 10.1038/nn.2249.10.1038/nn.2249PMC269474519169250Gan M, Jiang P, McLean P, Kanekiyo T, Bu G. Low-density lipoprotein receptor-related protein 1 (LRP1) regulates the stability and function of GluA1 α-amino-3-hydroxy-5-Methyl-4-isoxazole propionic acid (AMPA) receptor in neurons. PLoS One. 2014;9:e113237. doi: 10.1371/journal.pone.0113237.10.1371/journal.pone.0113237PMC426474625500815Kim E, Cho KO, Rothschild A, Sheng M. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Neuron. 1996;17:103–113. doi: 10.1016/S0896-6273(00)80284-6.10.1016/S0896-6273(00)80284-68755482Kruger JM, Favaro PD, Liu M, Kitlinska A, Huang X, Raabe M, Akad DS, Liu Y, Urlaub H, Dong Y, Xu W, Schlüter OM. Differential roles of postsynaptic density-93 isoforms in regulating synaptic transmission. J Neurosci. 2013;33:15504–15517. doi: 10.1523/JNEUROSCI.0019-12.2013.10.1523/JNEUROSCI.0019-12.2013PMC378262524068818Nada S, Shima T, Yanai H, Husi H, Grant SGN, Okada M, Akiyama T. Identification of PSD-93 as a substrate for the Src family tyrosine kinase Fyn. J Biol Chem. 2003;278:47610–47621. doi: 10.1074/jbc.M303873200.10.1074/jbc.M30387320013129934Sato Y, Tao YX, Su Q, Johns RA. Post-synaptic density-93 mediates tyrosine-phosphorylation of the N-methyl-d-aspartate receptors. Neuroscience. 2008;153:700–708. doi: 10.1016/j.neuroscience.2008.03.006.10.1016/j.neuroscience.2008.03.006PMC269605418423999Guo ML, Xue B, Jin DZ, Mao LM, Wang JQ. Interactions and phosphorylation of postsynaptic density 93 (PSD-93) by extracellular signal-regulated kinase (ERK) Brain Res. 2012;1465:18–25. doi: 10.1016/j.brainres.2012.05.026.10.1016/j.brainres.2012.05.026PMC338340322618309Aoki C, Miko I, Oviedo H, Mikeladze-Dvali T, Alexandre L, Sweeney N, Bredt DS. Electron microscopic immunocytochemical detection of PSD-95, PSD-93, SAP-102, and SAP-97 at postsynaptic, presynaptic, and nonsynaptic sites of adult and neonatal rat visual cortex. Synapse. 2001;40:239–257. doi: 10.1002/syn.1047.10.1002/syn.104711309840Sans N, Petralia RS, Wang Y, Ii JB, Hell JW, Wenthold RJ. A developmental change in NMDA receptor-associated proteins at hippocampal synapses. J Neurosci. 2000;20:1260–1271. doi: 10.1523/JNEUROSCI.20-03-01260.2000.10.1523/JNEUROSCI.20-03-01260.2000PMC677415810648730DeGiorgis JA, Galbraith JA, Dosemeci A, Chen X, Reese TS. Distribution of the scaffolding proteins PSD-95, PSD-93, and SAP97 in isolated PSDs. Brain Cell Biol. 2006;35:239–250. doi: 10.1007/s11068-007-9017-0.10.1007/s11068-007-9017-018392731Sun Q, Turrigiano GG. PSD-95 and PSD-93 play critical but distinct roles in synaptic scaling up and down. J Neurosci. 2011;31:6800–6808. doi: 10.1523/JNEUROSCI.5616-10.2011.10.1523/JNEUROSCI.5616-10.2011PMC311360721543610Brenman JE, Topinka JR, Cooper EC, McGee AW, Rosen J, Milroy T, Ralston HJ, Bredt DS. Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A. J Neurosci. 1998;18:8805–8813. doi: 10.1523/JNEUROSCI.18-21-08805.1998.10.1523/JNEUROSCI.18-21-08805.1998PMC67935509786987Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau LF, Veh RW, Huganir RL, Gundelfinger ED, Garner CC. SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo. Neuron. 1996;17:255–265. doi: 10.1016/S0896-6273(00)80157-9.10.1016/S0896-6273(00)80157-98780649Lau L, Mammen A, Ehlers MD, Kindler S, Chung WJ, Garner CC, Huganir RL. Interaction of the N-methyl-d-aspartate receptor complex with a novel synapse-associated protein, SAP102. J Biol Chem. 1996;271:21622–21628. doi: 10.1074/jbc.271.35.21622.10.1074/jbc.271.35.216228702950Cuthbert PC, Stanford LE, Coba MP, Ainge JA, Fink AE, Opazo P, Delgado JY, Komiyama NH, Dell TJO, Grant SGN. Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. J Neurosci. 2007;27:2673–2682. doi: 10.1523/JNEUROSCI.4457-06.2007.10.1523/JNEUROSCI.4457-06.2007PMC285114417344405Chen B, Thomas EV, Sanz-clemente A, Roche KW. NMDA receptor-dependent regulation of dendritic spine morphology by SAP102 splice variants. J Neurosci. 2011;31:89–96. doi: 10.1523/JNEUROSCI.1034-10.2011.10.1523/JNEUROSCI.1034-10.2011PMC303011921209193Chen BS, Gray JA, Sanz-Clemente A, Wei Z, Thomas EV, Nicoll RA, Roche KW. SAP102 mediates synaptic clearance of NMDA receptors. Cell Rep. 2012;2:1120–1128. doi: 10.1016/j.celrep.2012.09.024.10.1016/j.celrep.2012.09.024PMC351352523103165Elias GM, Elias LAB, Apostolides PF, Kriegstein AR, Nicoll RA. Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development. Proc Natl Acad Sci. 2008;105:20953–20958. doi: 10.1073/pnas.0811025106.10.1073/pnas.0811025106PMC263494419104036Bonnet SAD, Akad DS, Samaddar T, Liu Y, Huang X, Dong Y, Schlüter OM. Synaptic state-dependent functional interplay between postsynaptic density-95 and synapse-associated protein 102. J Neurosci. 2013;33:13398–13409. doi: 10.1523/JNEUROSCI.6255-11.2013.10.1523/JNEUROSCI.6255-11.2013PMC374292723946397Zheng C-Y, Petralia R, Wang Y, Kachar B, Wenthold RJ. SAP102 is a highly mobile MAGUK in spines. J Neurosci. 2010;30:4757–4766. doi: 10.1523/JNEUROSCI.6108-09.2010.10.1523/JNEUROSCI.6108-09.2010PMC287482620357126Zheng C, Wang Y, Kachar B, Petralia RS. Differential localization of SAP102 and PSD-95 is revealed in hippocampal spines using super- resolution light microscopy. Commun Integr Biol. 2011;0889:3–5.PMC307328721509195Wei Z, Wu G, Chen B. Regulation of SAP102 synaptic targeting by phosphorylation. Mol Neurobiol. 2018;55:6215–6226. doi: 10.1007/s12035-017-0836-4.10.1007/s12035-017-0836-4PMC659963129282697Lauks J, Klemmer P, Farzana F, Karupothula R, Zalm R, Cooke NE, Li KW, Smit AB, Toonen R, Verhage M. Synapse associated protein 102 (SAP102) binds the C-terminal part of the scaffolding protein neurobeachin. PLoS One. 2012;7:e39420. doi: 10.1371/journal.pone.0039420.10.1371/journal.pone.0039420PMC338000422745750Nair R, Lauks J, Jung SY, Cooke NE, de Wit H, Brose N, Kilimann MW, Verhage M, Rhee JS. Neurobeachin regulates neurotransmitter receptor trafficking to synapses. J Cell Biol. 2013;200:61–80. doi: 10.1083/jcb.201207113.10.1083/jcb.201207113PMC354279723277425Farzana F, Zalm R, Chen N, Li KW, Grant SGN, Smit AB, Toonen RF, Verhage M. Neurobeachin regulates glutamate- and GABA-receptor targeting to synapses via distinct pathways. Mol Neurobiol. 2016;53:2112–2123. doi: 10.1007/s12035-015-9164-8.10.1007/s12035-015-9164-8PMC482337925934101Murata Y, Constantine-Paton M. Postsynaptic density scaffold SAP102 regulates cortical synapse development through EphB and PAK signaling pathway. J Neurosci. 2013;33:5040–5052. doi: 10.1523/JNEUROSCI.2896-12.2013.10.1523/JNEUROSCI.2896-12.2013PMC363236523486974Levy JM, Chen X, Reese TS, Nicoll RA. Synaptic consolidation normalizes AMPAR quantal size following MAGUK loss. Neuron. 2015;87:534–548. doi: 10.1016/j.neuron.2015.07.015.10.1016/j.neuron.2015.07.015PMC459692326247861Chen X, Levy JM, Hou A, Winters C, Azzam R, Sousa AA, Leapman RD, Nicoll RA, Reese TS. PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density. Proc Natl Acad Sci. 2015;112:E6983–E6992. doi: 10.1073/pnas.1517045112.10.1073/pnas.1517045112PMC468759026604311Levy JM, Nicoll RA. Membrane-associated guanylate kinase dynamics reveal regional and developmental specificity of synapse stability. J Physiol. 2017;595:1699–1709. doi: 10.1113/JP273147.10.1113/JP273147PMC533087827861918Su D, Liu H, Liu T, Zhang X, Yang W, Song Y, Liu J, Wu Y, Chang L. Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages. J Anat. 2018;232:987–996. doi: 10.1111/joa.12807.10.1111/joa.12807PMC597981929574717Sans N, Racca C, Petralia RS, Wang YX, McCallum J, Wenthold RJ. Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway. J Neurosci. 2001;21:7506–7516. doi: 10.1523/JNEUROSCI.21-19-07506.2001.10.1523/JNEUROSCI.21-19-07506.2001PMC676290311567040Rumbaugh G, Sia G-M, Garner C, Huganir RL. Synapse-associated protein-97 isoform-specific regulation of surface AMPA receptors and synaptic function in cultured neurons. J Cell Biol. 2003;23:4567–4576.PMC674081012805297Waites CL, Specht CG, Hartel K, Leal-Ortiz S, Genoux D, Li D, Drisdel RC, Jeyifous O, Cheyne JE, Green WN, Montgomery JM, Garner CC. Synaptic SAP97 isoforms regulate AMPA receptor dynamics and access to presynaptic glutamate. J Neurosci. 2009;29:4332–4345. doi: 10.1523/JNEUROSCI.4431-08.2009.10.1523/JNEUROSCI.4431-08.2009PMC323053319357261Li D, Specht CG, Waites CL, Butler-Munro C, Leal-Ortiz S, Foote JW, Genoux D, Garner CC, Montgomery JM. SAP97 directs NMDA receptor spine targeting and synaptic plasticity. J Physiol. 2011;589:4491–4510. doi: 10.1113/jphysiol.2011.215566.10.1113/jphysiol.2011.215566PMC320822021768261Valtschanoff JG, Burette A, Davare MA, Soren Leonard A, Hell JW, Weinberg RJ. SAP97 concentrates at the postsynaptic density in cerebral cortex. Eur J Neurosci. 2000;12:3605–3614. doi: 10.1046/j.1460-9568.2000.00256.x.10.1046/j.1460-9568.2000.00256.x11029631Tully MD, Grossmann JG, Phelan M, Pandelaneni S, Leyland M, Lian LY. Conformational characterization of synapse-associated protein 97 by nuclear magnetic resonance and small-angle X-ray scattering shows compact and elongated forms. Biochemistry. 2012;51:899–908. doi: 10.1021/bi201178v.10.1021/bi201178v22242544Nakagawa T, Futai K, Lashuel HA, Lo I, Okamoto K, Walz T, Hayashi Y, Sheng M. Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Neuron. 2004;44:453–467. doi: 10.1016/j.neuron.2004.10.012.10.1016/j.neuron.2004.10.01215504326Goodman L, Baddeley D, Ambroziak W, Waites CL, Garner CC, Soeller C, Montgomery JM. N-terminal SAP97 isoforms differentially regulate synaptic structure and postsynaptic surface pools of AMPA receptors. Hippocampus. 2017;27:668–682. doi: 10.1002/hipo.22723.10.1002/hipo.2272328244171Klöcker N, Bunn RC, Schnell E, Caruana G, Bernstein A, Nicoll RA, Bredt DS. Synaptic glutamate receptor clustering in mice lacking the SH3 and GK domains of SAP97. Eur J Neurosci. 2002;16:1517–1522. doi: 10.1046/j.1460-9568.2002.02228.x.10.1046/j.1460-9568.2002.02228.x12405965Wu H, Nash JE, Zamorano P, Garner CC. Interaction of SAP97 with minus-end-directed actin motor myosin VI: implications for AMPA receptor trafficking. J Biol Chem. 2002;277:30928–30934. doi: 10.1074/jbc.M203735200.10.1074/jbc.M20373520012050163Nash JE, Appleby VJ, Corrêa SAL, Wu H, Fitzjohn SM, Garner CC, Collingridge GL, Molnár E. Disruption of the interaction between myosin VI and SAP97 is associated with a reduction in the number of AMPARs at hippocampal synapses. J Neurochem. 2010;112:677–690. doi: 10.1111/j.1471-4159.2009.06480.x.10.1111/j.1471-4159.2009.06480.x19895665Tavalin SJ, Colledge M, Hell JW, Langeberg LK, Huganir RL, Scott JD. Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depression. J Neurosci. 2002;22:3044–3051. doi: 10.1523/JNEUROSCI.22-08-03044.2002.10.1523/JNEUROSCI.22-08-03044.2002PMC675752711943807Mauceri D, Cattabeni F, Di Luca M, Gardoni F. Printed in calmodulin-dependent protein kinase II phosphorylation drives synapse-associated protein 97 into spines. J Biol Chem. 2004;279:23813–23821. doi: 10.1074/jbc.M402796200.10.1074/jbc.M40279620015044483Nikandrova YA, Jiao Y, Baucum AJ, Tavalin SJ, Colhran RJ. Ca2+/calmodulin-dependent protein kinase II binds to and phosphorylates a specific SAP97 splice variant to disrupt association with AKAP79/150 and modulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPAR) activity. J Biol Chem. 2010;285:923–934. doi: 10.1074/jbc.M109.033985.10.1074/jbc.M109.033985PMC280129319858198Zheng Z, Keifer J. Sequential delivery of synaptic GluA1- and GluA4-containing AMPa receptors (AMPARs) by SAP97 anchored protein complexes in classical conditioning. J Biol Chem. 2014;289:10540–10550. doi: 10.1074/jbc.M113.535179.10.1074/jbc.M113.535179PMC403617524567325Cai C, Li H, Rivera C, Keinänen K. Interaction between SAP97 and PSD-95, two Maguk proteins involved in synaptic trafficking of AMPA receptors. J Biol Chem. 2006;281:4267–4273. doi: 10.1074/jbc.M505886200.10.1074/jbc.M50588620016332687Howard MA, Elias GM, Elias LAB, Swat W, Nicoll RA. The role of SAP97 in synaptic glutamate receptor dynamics. Proc Natl Acad Sci. 2010;107:3805–3810. doi: 10.1073/pnas.0914422107.10.1073/pnas.0914422107PMC284052220133708Lin EI, Jeyifous O, Green WN. CASK regulates SAP97 conformation and its interactions with AMPA and NMDA receptors. J Neurosci. 2013;33:12067–12076. doi: 10.1523/JNEUROSCI.0816-13.2013.10.1523/JNEUROSCI.0816-13.2013PMC371373723864692Jeyifous O, Waites CL, Specht CG, Fujisawa S, Schubert M, Lin EI, Marshall J, Aoki C, de Silva T, Montgomery JM, Garner CC, Green WN, De Silva T, Johanna M. SAP97 and CASK mediate sorting of N-Methyl-D-Aspartate Receptors through a novel secretory pathway. Nat Neurosci. 2009;12:1011–1019. doi: 10.1038/nn.2362.10.1038/nn.2362PMC277905619620977Marcello E, Gardoni F, Mauceri D, Romorini S, Jeromin A, Epis R, Borroni B, Cattabeni F, Sala C, Padovani A, Di Luca M. Synapse-associated protein-97 mediates a-secretase ADAM10 trafficking and promotes its activity. J Neurosci. 2007;27:1682–1691. doi: 10.1523/JNEUROSCI.3439-06.2007.10.1523/JNEUROSCI.3439-06.2007PMC667374217301176Marcello E, Epis R, Saraceno C, Gardoni F, Borroni B, Cattabeni F, Padovani A, di Luca M. SAP97-mediated local trafficking is altered in Alzheimer disease patients’ hippocampus. Neurobiol Aging. 2012;33:422.e1–422.e10. doi: 10.1016/j.neurobiolaging.2010.09.015.10.1016/j.neurobiolaging.2010.09.01520980075Toyooka K, Iritani S, Makifuchi T, Shirakawa O, Kitamura N, Maeda K, Nakamura R, Niizato K, Watanabe M, Kakita A, Takahashi H, Someya T, Nawa H. Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia. J Neurochem. 2002;83:797–806. doi: 10.1046/j.1471-4159.2002.01181.x.10.1046/j.1471-4159.2002.01181.x12421351Regalado MP. Transsynaptic signaling by postsynaptic synapse-associated protein 97. J Neurosci. 2006;26:2343–2357. doi: 10.1523/JNEUROSCI.5247-05.2006.10.1523/JNEUROSCI.5247-05.2006PMC667480416495462Jing-Ping Z, Tian QB, Sakagami H, Kondo H, Endo S, Suzuki T. p55 protein is a member of PSD scaffold proteins in the rat brain and interacts with various PSD proteins. Mol Brain Res. 2005;135:204–216. doi: 10.1016/j.molbrainres.2004.12.023.10.1016/j.molbrainres.2004.12.02315857683Rademacher N, Schmerl B, Lardong JA, Wahl MC, Shoichet SA. MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density. Sci Rep. 2016;6:1–10. doi: 10.1038/srep35283.10.1038/srep35283PMC506948027756895Kim G, Luján R, Schwenk J, Kelley MH, Aguado C, Watanabe M, Fakler B, Maylie J, Adelman JP. Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function. Elife. 2016;5:1–18.PMC476456426880549Nakagawa T, Cheng Y, Sheng M, Walz T. Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins. Biol Chem. 2006;387:179–187. doi: 10.1515/BC.2006.024.10.1515/BC.2006.02416497150Kato AS, Gill MB, Yu H, Nisenbaum ES, Bredt DS. TARPs differentially decorate AMPA receptors to specify neuropharmacology. Trends Neurosci. 2010;33:241–248. doi: 10.1016/j.tins.2010.02.004.10.1016/j.tins.2010.02.00420219255Chen RS, Deng TC, Garcia T, Sellers ZM, Best PM. Calcium channel γ subunits: a functionally diverse protein family. Cell Biochem Biophys. 2007;47:178–186. doi: 10.1007/s12013-007-0002-0.10.1007/s12013-007-0002-017652770Menuz K, O’Brien JL, Karmizadegan S, Bredt DS, Nicoll RA. TARP redundancy is critical for maintaining AMPA receptor function. J Neurosci. 2008;28:8740–8746. doi: 10.1523/JNEUROSCI.1319-08.2008.10.1523/JNEUROSCI.1319-08.2008PMC315904118753375Menuz K, Kerchner GA, O’Brien JL, Nicoll RA. Critical role for TARPs in early development despite broad functional redundancy. Neuropharmacology. 2009;56:22–29. doi: 10.1016/j.neuropharm.2008.06.037.10.1016/j.neuropharm.2008.06.037PMC311109018634809Kim KS, Yan D, Tomita S. Assembly and stoichiometry of the AMPA receptor and TARP complex. J Neurosci. 2010;30:1064–1072. doi: 10.1523/JNEUROSCI.3909-09.2010.10.1523/JNEUROSCI.3909-09.2010PMC282115520089915Hastie P, Ulbrich MH, Wang H-L, Arant RJ, Lau AG, Zhang Z, Isacoff EY, Chen L. AMPA receptor/TARP stoichiometry visualized by single-molecule subunit counting. Proc Natl Acad Sci. 2013;110:5163–5168. doi: 10.1073/pnas.1218765110.10.1073/pnas.1218765110PMC361264223479622Shi Y, Lu W, Milstein AD, Nicoll RA. The stoichiometry of AMPA receptors and TARPs Varies by neuronal cell type. Neuron. 2009;62:633–640. doi: 10.1016/j.neuron.2009.05.016.10.1016/j.neuron.2009.05.016PMC311953119524523Tomita S, Chen L, Kawasaki Y, Petralia RS, Wenthold RJ, Nicoll RA, Bredt DS. Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins. J Cell Biol. 2003;161:805–816. doi: 10.1083/jcb.200212116.10.1083/jcb.200212116PMC219935412771129Letts VA, Felix R, Biddlecome GH, Arikkath J, Mahaffey CL, Valenzuela A, Bartlett FS, Mori Y, Campbell KP, Frankel WN. The mouse stargazer gene encodes a neuronal Ca2+-channel γ subunit. Nat Genet. 1998;19:340–347. doi: 10.1038/1228.10.1038/12289697694Bedoukian MA, Whitesell JD, Peterson EJ, Clay CM, Partin KM. The stargazin C terminus encodes an intrinsic and transferable membrane sorting signal. J Biol Chem. 2008;283:1597–1600. doi: 10.1074/jbc.M708141200.10.1074/jbc.M70814120017986442Jackson AC, Nicoll RA. The expanding social network of ionotropic glutamate receptors: TARPs and other transmembrane auxiliary subunits. Neuron. 2011;70:178–199. doi: 10.1016/j.neuron.2011.04.007.10.1016/j.neuron.2011.04.007PMC311951921521608Vandenberghe W, Nicoll RA, Bredt DS. Interaction with the unfolded protein response reveals a role for stargazin in biosynthetic AMPA receptor transport. J Neurosci. 2005;25:1095–1102. doi: 10.1523/JNEUROSCI.3568-04.2005.10.1523/JNEUROSCI.3568-04.2005PMC672594915689545Tomita S, Fukata M, Nicoll R, Bredt D. Dynamic interaction of stargazing-like TARPs with cycling AMPA receptors at synapses. Science. 2004;303:1508–1511. doi: 10.1126/science.1090262.10.1126/science.109026215001777Opazo P, Labrecque S, Tigaret CM, Frouin A, Wiseman PW, De Koninck P, Choquet D. CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin. Neuron. 2010;67:239–252. doi: 10.1016/j.neuron.2010.06.007.10.1016/j.neuron.2010.06.00720670832Constals A, Penn AC, Compans B, Toulmé E, Phillipat A, Marais S, Retailleau N, Hafner AS, Coussen F, Hosy E, Choquet D. Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from stargazin. Neuron. 2015;85:787–803. doi: 10.1016/j.neuron.2015.01.012.10.1016/j.neuron.2015.01.01225661182Matsuda S, Kakegawa W, Budisantoso T, Nomura T, Kohda K, Yuzaki M. Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression. Nat Commun. 2013;4:1–15. doi: 10.1038/ncomms3759.10.1038/ncomms375924217640Stein ELA, Chetkovich DM. Regulation of stargazin synaptic trafficking by C-terminal PDZ ligand phosphorylation in bidirectional synaptic plasticity. J Neurochem. 2010;113:42–53. doi: 10.1111/j.1471-4159.2009.06529.x.10.1111/j.1471-4159.2009.06529.xPMC403548319968761Nomura T, Kakegawa W, Matsuda S, Kohda K, Nishiyama J, Takahashi T, Yuzaki M. Cerebellar long-term depression requires dephosphorylation of TARP in Purkinje cells. Eur J Neurosci. 2012;35:402–410. doi: 10.1111/j.1460-9568.2011.07963.x.10.1111/j.1460-9568.2011.07963.x22239345Louros SR, Hooks BM, Litvina L, Carvalho AL, Chen C. A role for stargazin in experience-dependent plasticity. Cell Rep. 2014;7:1614–1625. doi: 10.1016/j.celrep.2014.04.054.10.1016/j.celrep.2014.04.054PMC411513024882000Louros SR, Caldeira GL, Carvalho AL. Stargazin dephosphorylation mediates homeostatic synaptic downscaling of excitatory synapses. Front Mol Neurosci. 2018;11:1–13. doi: 10.3389/fnmol.2018.00328.10.3389/fnmol.2018.00328PMC614602830271322Chen L, El-Husseini A, Tomita S, Bredt DS, Nicoll R. Stargazin differentially controls the trafficking of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate and kainate receptors. Mol Pharmacol. 2003;64:703–706. doi: 10.1124/mol.64.3.703.10.1124/mol.64.3.70312920207Tomita S, Adesnik H, Sekiguchi M, Zhang W, Wada K, Howe JR, Nicoll RA, Bredt DS. Stargazin modulates AMPA receptor gating and trafficking by distinct domains. Nature. 2005;435:1052–1058. doi: 10.1038/nature03624.10.1038/nature0362415858532Turetsky D, Garringer E, Patneau D. Stargazin modulates native AMPA receptor functional properties by two distinct mechanisms. J Neurosci. 2005;25:7438–7448. doi: 10.1523/JNEUROSCI.1108-05.2005.10.1523/JNEUROSCI.1108-05.2005PMC672529816093395Bedoukian MA, Weeks AM, Partin KM. Different domains of the AMPA receptor direct stargazin-mediated trafficking and stargazin-mediated modulation of kinetics. J Biol Chem. 2006;281:23908–23921. doi: 10.1074/jbc.M600679200.10.1074/jbc.M60067920016793768Tomita S, Shenoy A, Fukata Y, Nicoll RA, Bredt DS. Stargazin interacts functionally with the AMPA receptor glutamate-binding module. Neuropharmacology. 2007;52:87–91. doi: 10.1016/j.neuropharm.2006.07.012.10.1016/j.neuropharm.2006.07.01216919685Roberts MF, Taylor D, Unger V. Two modes of interaction between the membrane-embedded TARP stargazin’s C-terminal domain and the bilayer visualized by electron crystallography. J Struct Biol. 2011;174:542–551. doi: 10.1016/j.jsb.2011.03.012.10.1016/j.jsb.2011.03.012PMC309195621426941Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI. Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy. Science. 2016;353:975–1008. doi: 10.1126/science.aaf8411.10.1126/science.aaf8411PMC512525527365450Zhao Y, Chen S, Yoshioka C, Baconguis I, Gouaux E. Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM. Nature. 2016;536:108–111. doi: 10.1038/nature18961.10.1038/nature18961PMC499897227368053Shaikh SA, Dolino DM, Lee G, Chatterjee S, MacLean DM, Flatebo C, Landes CF, Jayaraman V. Stargazin modulation of AMPA receptors. Cell Rep. 2016;17:328–335. doi: 10.1016/j.celrep.2016.09.014.10.1016/j.celrep.2016.09.014PMC508878227705782Ben-Yaacov A, Gillor M, Haham T, Parsai A, Qneibi M, Stern-Bach Y. Molecular mechanism of AMPA receptor modulation by TARP/stargazin. Neuron. 2017;93:1126–1137.e4. doi: 10.1016/j.neuron.2017.01.032.10.1016/j.neuron.2017.01.03228238551Chen S, Zhao Y, Wang Y, Shekhar M, Tajkhorshid E, Gouaux E. Activation and desensitization mechanism of AMPA receptor–TARP complex by cryo-EM. Cell. 2017;170:1234–1246.e14. doi: 10.1016/j.cell.2017.07.045.10.1016/j.cell.2017.07.045PMC562184128823560Shanks NF, Maruo T, Farina AN, Ellisman MH, Nakagawa T. Contribution of the global subunit structure and stargazin on the maturation of AMPA receptors. J Neurosci. 2010;30:2728–2740. doi: 10.1523/JNEUROSCI.5146-09.2010.10.1523/JNEUROSCI.5146-09.2010PMC284290820164357Ives JH, Fung S, Tiwari P, Payne HL, Thompson CL. Microtubule-associated protein light chain 2 is a stargazin-AMPA receptor complex-interacting protein in vivo. J Biol Chem. 2004;279:31002–31009. doi: 10.1074/jbc.M402214200.10.1074/jbc.M40221420015136571Cuadra AE, Kuo S-H, Kawasaki Y, Bredt D, Chetkovich D. AMPA receptor synaptic targeting regulated by stargazin interactions with the Golgi-resident PDZ protein nPIST. J Neurosci. 2004;24:7491–7502. doi: 10.1523/JNEUROSCI.1255-04.2004.10.1523/JNEUROSCI.1255-04.2004PMC672963715329396Hafner AS, Penn AC, Grillo-Bosch D, Retailleau N, Poujol C, Philippat A, Coussen F, Sainlos M, Opazo P, Choquet D. Lengthening of the stargazin cytoplasmic tail increases synaptic transmission by promoting interaction to deeper domains of PSD-95. Neuron. 2015;86:475–489. doi: 10.1016/j.neuron.2015.03.013.10.1016/j.neuron.2015.03.01325843401Chetkovich DM, Chen L, Stocker TJ, Nicoll R, Bredt DS. Phosphorylation of the postsynaptic density-95 (PSD-95)/discs large/zona occludens-1 binding site of stargazin regulates binding to PSD-95 and synaptic targeting of AMPA receptors. J Neurosci. 2002;22:5791–5796. doi: 10.1523/JNEUROSCI.22-14-05791.2002.10.1523/JNEUROSCI.22-14-05791.2002PMC675793412122038Choi J, Ko J, Park E, Lee JR, Yoon J, Lim S, Kim E. Phosphorylation of stargazin by protein kinase A regulates its interaction with PSD-95. J Biol Chem. 2002;277:12359–12363. doi: 10.1074/jbc.M200528200.10.1074/jbc.M20052820011805122Tomita S, Stein V, Stocker TJ, Nicoll RA, Bredt DS. Bidirectional synaptic plasticity regulated by phosphorylation of stargazin-like TARPs. Neuron. 2005;45:269–277. doi: 10.1016/j.neuron.2005.01.009.10.1016/j.neuron.2005.01.00915664178Sumioka A, Yan D, Tomita S. TARP phosphorylation regulates synaptic AMPA receptors through lipid bilayers. Neuron. 2010;66:755–767. doi: 10.1016/j.neuron.2010.04.035.10.1016/j.neuron.2010.04.035PMC288769420547132Tsui J, Malenka RC. Substrate localization creates specificity in calcium/calmodulin-dependent protein kinase II signaling at synapses. J Biol Chem. 2006;281:13794–13804. doi: 10.1074/jbc.M600966200.10.1074/jbc.M60096620016551613Nakagawa T, Cheng Y, Ramm E, Sheng M, Walz T. Structure and different conformational states of native AMPA receptor complexes. Nature. 2005;433:545–549. doi: 10.1038/nature03328.10.1038/nature0332815690046Selvakumar B, Huganir RL, Snyder SH. S-nitrosylation of stargazin regulates surface expression of AMPA-glutamate neurotransmitter receptors. Proc Natl Acad Sci. 2009;106:16440–16445. doi: 10.1073/pnas.0908949106.10.1073/pnas.0908949106PMC275252319805317Zheng C-Y, Chang K, Suh YH, Roche KW. TARP γ-8 glycosylation regulates the surface expression of AMPA receptors. Biochem J. 2015;465:471–477. doi: 10.1042/BJ20140806.10.1042/BJ2014080625495042Tao Y, Chen YJ, Shen C, Luo Z, Bates CR, Lee D, Marchetto S, Gao TM, Borg JP, Xiong WC, Mei L. Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons. Nat Neurosci. 2013;16:290–299. doi: 10.1038/nn.3320.10.1038/nn.332023354328Adotevi NK, Leitch B. Alterations in AMPA receptor subunit expression in cortical inhibitory interneurons in the epileptic stargazer mutant mouse. Neuroscience. 2016;339:124–138. doi: 10.1016/j.neuroscience.2016.09.052.10.1016/j.neuroscience.2016.09.05227717808Adotevi NK, Leitch B. Synaptic changes in AMPA receptor subunit expression in cortical parvalbumin interneurons in the stargazer model of absence epilepsy. Front Mol Neurosci. 2017;10:1–10. doi: 10.3389/fnmol.2017.00434.10.3389/fnmol.2017.00434PMC574407329311821Kessels HW, Kopec CD, Klein ME, Malinow R. Roles of stargazin and phosphorylation in the control of AMPA receptor subcellular distribution. Nat Neurosci. 2009;12:888–896. doi: 10.1038/nn.2340.10.1038/nn.2340PMC392270619543281Deng F, Price MG, Davis CF, Mori M, Burgess DL. Stargazin and other transmembrane AMPA receptor regulating proteins interact with synaptic scaffolding protein MAGI-2 in brain. J Neurosci. 2006;26:7875–7884. doi: 10.1523/JNEUROSCI.1851-06.2006.10.1523/JNEUROSCI.1851-06.2006PMC667423016870733Hamad MIK, Jack A, Klatt O, Lorkowski M, Strasdeit T, Kott S, Sager C, Hollmann M, Wahle P. Type I TARPs promote dendritic growth of early postnatal neocortical pyramidal cells in organotypic cultures. Development. 2014;141:1737–1748. doi: 10.1242/dev.099697.10.1242/dev.09969724667327Letts VA, Mahaffey CL, Beyer B, Frankel WN. A targeted mutation in Cacng4 exacerbates spike-wave seizures in stargazer (Cacng2) mice. Proc Natl Acad Sci. 2005;102:2123–2128. doi: 10.1073/pnas.0409527102.10.1073/pnas.0409527102PMC54857415677329Korber C, Werner M, Kott S, Ma Z-L, Hollmann M. The transmembrane AMPA receptor regulatory protein γ4 is a more effective modulator of AMPA receptor function than stargazin (γ2) J Neurosci. 2007;27:8442–8447. doi: 10.1523/JNEUROSCI.0424-07.2007.10.1523/JNEUROSCI.0424-07.2007PMC667305117670991Ferrario CR, Loweth JA, Milovanovic M, Wang X, Wolf ME. Distribution of AMPA receptor subunits and TARPs in synaptic and extrasynaptic membranes of the adult rat nucleus accumbens. Neurosci Lett. 2011;490:180–184. doi: 10.1016/j.neulet.2010.12.036.10.1016/j.neulet.2010.12.036PMC303818321182898Sumioka A, Brown TE, Kato AS, Bredt DS, Kauer JA, Tomita S. PDZ binding of TARPγ-8 controls synaptic transmission but not synaptic plasticity. Nat Neurosci. 2011;14:1410–1412. doi: 10.1038/nn.2952.10.1038/nn.2952PMC320664422002768Fukaya M, Tsujita M, Yamazaki M, Kushiya E, Abe M, Akashi K, Natsume R, Kano M, Kamiya H, Watanabe M, Sakimura K. Abundant distribution of TARP γ-8 in synaptic and extrasynaptic surface of hippocampal neurons and its major role in AMPA receptor expression on spines and dendrites. Eur J Neurosci. 2006;24:2177–2190. doi: 10.1111/j.1460-9568.2006.05081.x.10.1111/j.1460-9568.2006.05081.x17074043Yamasaki M, Fukaya M, Yamazaki M, Azechi H, Natsume R, Abe M, Sakimura K, Watanabe M. TARP γ-2 and γ-8 differentially control AMPAR density across schaffer collateral/commissural synapses in the hippocampal CA1 area. J Neurosci. 2016;36:4296–4312. doi: 10.1523/JNEUROSCI.4178-15.2016.10.1523/JNEUROSCI.4178-15.2016PMC660177527076426Milstein AD, Nicoll RA. TARP modulation of synaptic AMPA receptor trafficking and gating depends on multiple intracellular domains. Proc Natl Acad Sci. 2009;106:11348–11351. doi: 10.1073/pnas.0905570106.10.1073/pnas.0905570106PMC270876719549880Sheng N, Bemben MA, Díaz-Alonso J, Tao W, Shi YS, Nicoll RA. LTP requires postsynaptic PDZ-domain interactions with glutamate receptor/auxiliary protein complexes. Proc Natl Acad Sci. 2018;115:3948–3953. doi: 10.1073/pnas.1800719115.10.1073/pnas.1800719115PMC589949029581259Inamura M, Itakura M, Okamoto H, Hoka S, Mizoguchi A, Fukazawa Y, Shigemoto R, Yamamori S, Takahashi M. Differential localization and regulation of stargazin-like protein, γ-8 and stargazin in the plasma membrane of hippocampal and cortical neurons. Neurosci Res. 2006;55:45–53. doi: 10.1016/j.neures.2006.01.004.10.1016/j.neures.2006.01.00416516319Park J, Chávez AE, Mineur YS, Morimoto-Tomita M, Lutzu S, Kim KS, Picciotto MR, Castillo PE, Tomita S. CaMKII phosphorylation of TARPγ-8 is a mediator of LTP and learning and memory. Neuron. 2016;92:75–83. doi: 10.1016/j.neuron.2016.09.002.10.1016/j.neuron.2016.09.002PMC505984627667007Itakura M, Watanabe I, Sugaya T, Takahashi M. Direct association of the unique C-terminal tail of transmembrane AMPA receptor regulatory protein γ-8 with calcineurin. FEBS J. 2014;281:1366–1378. doi: 10.1111/febs.12708.10.1111/febs.1270824418105Moss FJ, Viard P, Davies A, Bertaso F, Page KM, Graham A, Canti C, Plumpton M, Plumpton C, Clare JJ, Dolphin AC. The novel product of a five-exon stargazin-related gene abolishes Cav2.2 calcium channel expression. EMBO J. 2002;21:1514–1523. doi: 10.1093/emboj/21.7.1514.10.1093/emboj/21.7.1514PMC12536311927536Kato AS, Zhou W, Milstein AD, Knierman MD, Siuda ER, Dotzlaf JE, Yu H, Hale JE, Nisenbaum ES, Nicoll RA, Bredt DS. New transmembrane AMPA receptor regulatory protein isoform, γ-7, differentially regulates AMPA receptors. J Neurosci. 2007;27:4969–4977. doi: 10.1523/JNEUROSCI.5561-06.2007.10.1523/JNEUROSCI.5561-06.2007PMC667208417475805Yamazaki M, Fukaya M, Hashimoto K, Yamasaki M, Tsujita M, Itakura M, Abe M, Natsume R, Takahashi M, Kano M, Sakimura K, Watanabe M. TARPs γ-2 and γ-7 are essential for AMPA receptor expression in the cerebellum. Eur J Neurosci. 2010;31:2204–2220. doi: 10.1111/j.1460-9568.2010.07254.x.10.1111/j.1460-9568.2010.07254.x20529126Kato AS, Siuda ER, Nisenbaum ES, Bredt DS. AMPA receptor subunit-specific regulation by a distinct family of type II TARPs. Neuron. 2008;59:986–996. doi: 10.1016/j.neuron.2008.07.034.10.1016/j.neuron.2008.07.03418817736Yamazaki M, Le Pichon CE, Jackson AC, Cerpas M, Sakimura K, Scearce-Levie K, Nicoll RA. Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior. Proc Natl Acad Sci. 2015;112:E371–E379. doi: 10.1073/pnas.1423670112.10.1073/pnas.1423670112PMC431385125583485Bats C, Soto D, Studniarczyk D, Farrant M, Cull-Candy SG. Channel properties reveal differential expression of TARPed and TARPless AMPARs in stargazer neurons. Nat Neurosci. 2012;15:853–861. doi: 10.1038/nn.3107.10.1038/nn.3107PMC342701122581185Studniarczyk D, Coombs I, Cull-Candy SG, Farrant M. TARP γ-7 selectively enhances synaptic expression of calcium-permeable AMPARs. Nat Neurosci. 2013;16:1266–1274. doi: 10.1038/nn.3473.10.1038/nn.3473PMC385865123872597Ferron L, Davies A, Page KM, Cox DJ, Leroy J, Waithe D, Butcher AJ, Sellaturay P, Bolsover S, Pratt WS, Moss FJ, Dolphin AC. The stargazin-related protein γ7 interacts with the mRNA-binding protein heterogeneous nuclear ribonucleoprotein A2 and regulates the stability of specific mRNAs, including CaV2.2. J Neurosci. 2008;28:10604–10617. doi: 10.1523/JNEUROSCI.2709-08.2008.10.1523/JNEUROSCI.2709-08.2008PMC266959318923037Waithe D, Ferron L, Dolphin AC. Stargazin-related protein γ7 is associated with signalling endosomes in superior cervical ganglion neurons and modulates neurite outgrowth. J Cell Sci. 2011;124:2049–2057. doi: 10.1242/jcs.084988.10.1242/jcs.084988PMC310403521610096Ashburner M, Thompson P, Roote J, Lasko PF, Grau Y, El Messal M, Roth S, Simpson P. The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. VII. Characterization of the region around the snail and cactus loci. Genetics. 1990;126:679–694.PMC12042232123463Schwenk J, Harmel N, Zolles G, Bildl W, Kulik A, Heimrich B, Chisaka O, Jonas P, Schulte U, Fakler B, Klöcker N. Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors. Science. 2009;323:1313–1320. doi: 10.1126/science.1167852.10.1126/science.116785219265014Mauric V, Mölders A, Harmel N, Heimrich B, Sergeeva OA, Klöcker N. Ontogeny repeats the phylogenetic recruitment of the cargo exporter cornichon into AMPA receptor signaling complexes. Mol Cell Neurosci. 2013;56:10–17. doi: 10.1016/j.mcn.2013.02.001.10.1016/j.mcn.2013.02.00123403072Kato AS, Gill MB, Ho MT, Yu H, Tu Y, Siuda ER, Wang H, Qian YW, Nisenbaum ES, Tomita S, Bredt DS. Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins. Neuron. 2010;68:1082–1096. doi: 10.1016/j.neuron.2010.11.026.10.1016/j.neuron.2010.11.026PMC303422221172611Shi Y, Suh YH, Milstein AD, Isozaki K, Schmid SM, Roche KW, Nicoll RA. Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating. Proc Natl Acad Sci. 2010;107:16315–16319. doi: 10.1073/pnas.1011706107.10.1073/pnas.1011706107PMC294134020805473Harmel N, Cokic B, Zolles G, Berkefeld H, Mauric V, Fakler B, Stein V, Klöcker N. AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling. PLoS One. 2012;7:e30681. doi: 10.1371/journal.pone.0030681.10.1371/journal.pone.0030681PMC326551222292017Brockie PJ, Jensen M, Mellem JE, Jensen E, Yamasaki T, Wang R, Thacker C, Maxfield D, Hoerndli F, Dunn Patrick J, Tomita S, Madsen DM, Maricq AV. Cornichons control ER export of AMPA receptors to regulate synaptic excitability. Neuron. 2013;80:129–142. doi: 10.1016/j.neuron.2013.07.028.10.1016/j.neuron.2013.07.028PMC379543924094107Gill MB, Kato AS, Roberts MF, Yu H, Wang H, Tomita S, Bredt DS. Cornichon-2 modulates AMPA receptor-transmembrane AMPA receptor regulatory protein assembly to dictate gating and pharmacology. J Neurosci. 2011;31:6928–6938. doi: 10.1523/JNEUROSCI.6271-10.2011.10.1523/JNEUROSCI.6271-10.2011PMC456241621543622Gill MB, Kato AS, Wang H, Bredt DS. AMPA receptor modulation by cornichon-2 dictated by transmembrane AMPA receptor regulatory protein isoform. Eur J Neurosci. 2012;35:182–194. doi: 10.1111/j.1460-9568.2011.07948.x.10.1111/j.1460-9568.2011.07948.x22211840Herring BE, Shi Y, Suh YH, Zheng C-Y, Blankenship SM, Roche KW, Nicoll RA. Cornichon proteins determine the subunit composition of synaptic AMPA receptors. Neuron. 2013;77:1083–1096. doi: 10.1016/j.neuron.2013.01.017.10.1016/j.neuron.2013.01.017PMC365256623522044Coombs ID, Soto D, Zonouzi M, Renzi M, Shelley C, Farrant M, Cull-Candy SG. Cornichons modify channel properties of recombinant and glial AMPA receptors. J Neurosci. 2012;32:9796–9804. doi: 10.1523/JNEUROSCI.0345-12.2012.10.1523/JNEUROSCI.0345-12.2012PMC342887422815494Boudkkazi S, Brechet A, Schwenk J, Fakler B. Cornichon2 dictates the time course of excitatory transmission at individual hippocampal synapses. Neuron. 2014;82:848–858. doi: 10.1016/j.neuron.2014.03.031.10.1016/j.neuron.2014.03.03124853943Shanks NF, Cais O, Maruo T, Savas JN, Zaika EI, Azumaya CM, Yates JR, Greger I, Nakagawa T. Molecular dissection of the interaction between the AMPA receptor and cornichon homolog-3. J Neurosci. 2014;34:12104–12120. doi: 10.1523/JNEUROSCI.0595-14.2014.10.1523/JNEUROSCI.0595-14.2014PMC415260825186755Hawken NM, Zaika EI, Nakagawa T. Engineering defined membrane-embedded elements of AMPA receptor induces opposing gating modulation by cornichon 3 and stargazin. J Physiol. 2017;595:6517–6539. doi: 10.1113/JP274897.10.1113/JP274897PMC563888928815591Schober DA, Gill MB, Yu H, Gernert DL, Jeffries MW, Ornstein PL, Kato AS, Felder CC, Bredt DS. Transmembrane AMPA receptor regulatory proteins and Cornichon-2 allosterically regulate AMPA receptor antagonists and potentiators. J Biol Chem. 2011;286:13134–13142. doi: 10.1074/jbc.M110.212522.10.1074/jbc.M110.212522PMC307566021343286Shanks NF, Savas JN, Maruo T, Cais O, Hirao A, Oe S, Ghosh A, Noda Y, Greger IH, Yates JR, Nakagawa T. Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L. Cell Rep. 2012;1:590–598. doi: 10.1016/j.celrep.2012.05.004.10.1016/j.celrep.2012.05.004PMC340196822813734Gu X, Mao X, Lussier MP, Hutchison MA, Zhou L, Hamra FK, Roche KW, Lu W. GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons. Nat Commun. 2016;7:1–18.PMC477806426932439Mao X, Gu X, Lu W. GSG1L regulates the strength of AMPA receptor-mediated synaptic transmission but not AMPA receptor kinetics in hippocampal dentate granule neurons. J Neurophysiol. 2017;117:28–35. doi: 10.1152/jn.00307.2016.10.1152/jn.00307.2016PMC520954227707810Keifer J, Tiwari NK, Buse L, Zheng Z. Subunit-specific synaptic delivery of AMPA receptors by auxiliary chaperone proteins TARPγ8 and GSG1L in classical conditioning. Neurosci Lett. 2017;645:53–59. doi: 10.1016/j.neulet.2017.02.041.10.1016/j.neulet.2017.02.041PMC539052528219790Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI. Channel opening and gating mechanism in AMPA-subtype glutamate receptors. Nature. 2017;549:60–65. doi: 10.1038/nature23479.10.1038/nature23479PMC574320628737760Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI. Structural bases of desensitization in AMPA receptor-auxiliary subunit complexes. Neuron. 2017;94:569–580.e5. doi: 10.1016/j.neuron.2017.04.025.10.1016/j.neuron.2017.04.025PMC549297528472657Pei J, Grishin NV. Unexpected diversity in Shisa-like proteins suggests the importance of their roles as transmembrane adaptors. Cell Signal. 2012;24:758–769. doi: 10.1016/j.cellsig.2011.11.011.10.1016/j.cellsig.2011.11.011PMC329559522120523von Engelhardt J, Mack V, Sprengel R, Kavenstock N, Li KW, Stern-Bach Y, Smit AB, Seeburg PH, Monyer H. CKAMP44: a brain-specific protein attenuating short-term synaptic plasticity in the dentate gyrus. Science. 2010;60:1518–1522. doi: 10.1126/science.1184178.10.1126/science.118417820185686Farrow P, Khodosevich K, Sapir Y, Schulmann A, Aslam M, Stern-Bach Y, Monyer H, von Engelhardt J. Auxiliary subunits of the CKAMP family differentially modulate AMPA receptor properties. Elife. 2015;4:1–16. doi: 10.7554/eLife.09693.10.7554/eLife.09693PMC473303526623514Khodosevich K, Jacobi E, Farrow P, Schulmann A, Rusu A, Zhang L, Sprengel R, Monyer H, von Engelhardt J. Coexpressed auxiliary subunits exhibit distinct modulatory profiles on AMPA receptor function. Neuron. 2014;83:601–615. doi: 10.1016/j.neuron.2014.07.004.10.1016/j.neuron.2014.07.00425066086Chen X, Aslam M, Gollisch T, Allen K, Von Engelhardt J. CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus. Nat Commun. 2018;9:1–13. doi: 10.1038/s41467-017-02088-w.10.1038/s41467-017-02088-wPMC577247029343769Karataeva AR, Klaassen RV, Ströder J, Ruiperez-Alonso M, Hjorth JJJ, Van Nierop P, Spijker S, Mansvelder HD, Smit AB. C-terminal interactors of the AMPA receptor auxiliary subunit Shisa9. PLoS One. 2014;9:e99280. doi: 10.1371/journal.pone.0087360.10.1371/journal.pone.0087360PMC391195324498314Kunde SA, Rademacher N, Zieger H, Shoichet SA. Protein kinase C regulates AMPA receptor auxiliary protein Shisa9/CKAMP44 through interactions with neuronal scaffold PICK1. FEBS Open Bio. 2017;7:1234–1245. doi: 10.1002/2211-5463.12261.10.1002/2211-5463.12261PMC558633928904854Klaassen RV, Stroeder J, Coussen F, Hafner AS, Petersen JD, Renancio C, Schmitz LJM, Normand E, Lodder JC, Rotaru DC, Rao-Ruiz P, Spijker S, Mansvelder HD, Choquet D, Smit AB. Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity. Nat Commun. 2016;7:1–12. doi: 10.1038/ncomms10682.10.1038/ncomms10682PMC477803526931375Schmitz LJM, Klaassen RV, Ruiperez-Alonso M, Zamri AE, Stroeder J, Rao-Ruiz P, Lodder JC, van der Loo RJ, Mansvelder HD, Smit AB, Spijker S. The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory. Elife. 2017;6:1–28. doi: 10.7554/eLife.24192.10.7554/eLife.24192PMC573765929199957de Wit J, Sylwestrak E, O’Sullivan ML, Otto S, Tiglio K, Savas JN, Yates JR, Comoletti D, Taylor P, Ghosh A. LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation. Neuron. 2009;64:799–806. doi: 10.1016/j.neuron.2009.12.019.10.1016/j.neuron.2009.12.019PMC282966620064388Laurén J, Airaksinen MS, Saarma M, Timmusk T. A novel gene family encoding leucine-rich repeat transmembrane proteins differentially expressed in the nervous system. Genomics. 2003;81:411–421. doi: 10.1016/S0888-7543(03)00030-2.10.1016/S0888-7543(03)00030-212676565Roppongi RT, Karimi B, Siddiqui TJ. Role of LRRTMs in synapse development and plasticity. Neurosci Res. 2017;116:18–28. doi: 10.1016/j.neures.2016.10.003.10.1016/j.neures.2016.10.00327810425Linhoff MW, Laurén J, Cassidy RM, Dobie FA, Takahashi H, Nygaard HB, Airaksinen MS, Strittmatter SM, Craig AM. An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers. Neuron. 2009;61:734–749. doi: 10.1016/j.neuron.2009.01.017.10.1016/j.neuron.2009.01.017PMC274610919285470Ko J, Fuccillo MV, Malenka RC, Südhof TC. LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation. Neuron. 2009;64:791–798. doi: 10.1016/j.neuron.2009.12.012.10.1016/j.neuron.2009.12.012PMC282931420064387Um JW, Choi TY, Kang H, Cho YS, Choii G, Uvarov P, Park D, Jeong D, Jeon S, Lee D, Kim H, Lee SH, Bae YC, Choi SY, Airaksinen MS, Ko J. LRRTM3 regulates excitatory synapse development through alternative splicing and neurexin binding. Cell Rep. 2016;14:808–822. doi: 10.1016/j.celrep.2015.12.081.10.1016/j.celrep.2015.12.08126776509de Wit J, O’Sullivan ML, Savas JN, Condomitti G, Caccese MC, Vennekens KM, Yates JR, Ghosh A. Unbiased discovery of Glypican as a receptor for LRRTM4 in regulating excitatory synapse development. Neuron. 2013;79:696–711. doi: 10.1016/j.neuron.2013.06.049.10.1016/j.neuron.2013.06.049PMC400352723911103Ko JS, Pramanik G, Um JW, Shim JS, Lee D, Kim KH, Chung G-Y, Condomitti G, Kim HM, Kim H, de Wit J, Park K-S, Tabuchi K, Ko J. PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission. Proc Natl Acad Sci. 2015;112:1874–1879. doi: 10.1073/pnas.1410138112.10.1073/pnas.1410138112PMC433073625624497Siddiqui TJ, Pancaroglu R, Kang Y, Rooyakkers A, Craig AM. LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development. J Neurosci. 2010;30:7495–7506. doi: 10.1523/JNEUROSCI.0470-10.2010.10.1523/JNEUROSCI.0470-10.2010PMC289626920519524Siddiqui TJ, Tari PK, Connor SA, Zhang P, Dobie FA, She K, Kawabe H, Wang YT, Brose N, Craig AM. An LRRTM4–HSPG complex mediates excitatory synapse development on dentate gyrus granule cells. Neuron. 2013;79:680–695. doi: 10.1016/j.neuron.2013.06.029.10.1016/j.neuron.2013.06.02923911104Soler-Llavina GJ, Arstikaitis P, Morishita W, Ahmad M, Südhof TC, Malenka RC. Leucine-rich repeat transmembrane proteins are essential for maintenance of long-term potentiation. Neuron. 2013;79:439–446. doi: 10.1016/j.neuron.2013.06.007.10.1016/j.neuron.2013.06.007PMC374166723931994Bhouri M, Morishita W, Temkin P, Goswami D, Kawabe H, Brose N, Südhof TC, Craig AM, Siddiqui TJ, Malenka R. Deletion of LRRTM1 and LRRTM2 in adult mice impairs basal AMPA receptor transmission and LTP in hippocampal CA1 pyramidal neurons. Proc Natl Acad Sci. 2018;115:201803280. doi: 10.1073/pnas.1803280115.10.1073/pnas.1803280115PMC600333629784826Sällman Almén M, Bringeland N, Fredriksson R, Schiöth HB. The dispanins: a novel gene family of ancient origin that contains 14 human members. PLoS One. 2012;7:e31961. doi: 10.1371/journal.pone.0031961.10.1371/journal.pone.0031961PMC328279622363774Kirk LM, Ti SW, Bishop HI, Orozco-Llamas M, Pham M, Trimmer JS, Díaz E. Distribution of the SynDIG4/proline-rich transmembrane protein 1 in rat brain. J Comp Neurol. 2016;524:2266–2280. doi: 10.1002/cne.23945.10.1002/cne.23945PMC489294326660156Kalashnikova E, Lorca RA, Kaur I, Barisone GA, Li B, Ishimaru T, Trimmer JS, Mohapatra DP, Diaz SynDIG1: an activity-regulated AMPA receptor-interacting transmembrane protein that regulates excitatory synapse development. Neuron. 2010;65:80–93. doi: 10.1016/j.neuron.2009.12.021.10.1016/j.neuron.2009.12.021PMC282272820152115Kaur I, Yarov-Yarovoy V, Kirk LM, Plambeck KE, Barragan EV, Ontiveros ES, Diaz E. Activity-dependent palmitoylation controls SynDIG1 stability, localization, and function. J Neurosci. 2016;36:7562–7568. doi: 10.1523/JNEUROSCI.4859-14.2016.10.1523/JNEUROSCI.4859-14.2016PMC495157027445135Rossi P, Sterlini B, Castroflorio E, Marte A, Onofri F, Valtorta F, Maragliano L, Corradi A, Benfenati F. A novel topology of proline-rich transmembrane protein 2 (PRRT2): hints for an intracellular function at the synapse. J Biol Chem. 2016;291:6111–6123. doi: 10.1074/jbc.M115.683888.10.1074/jbc.M115.683888PMC481355326797119Chenaux G, Matt L, Hill TC, Kaur I, Liu X-B, Kirk LM, Speca DJ, McMahon SA, Zito K, Hell JW, Diaz E. Loss of SynDIG1 reduces excitatory synapse maturation but not formation in vivo. eNeuro. 2016;3:ENEURO.0130-16.2016. doi: 10.1523/ENEURO.0130-16.2016.10.1523/ENEURO.0130-16.2016PMC507324827800545Lovero KL, Blankenship SM, Shi Y, Nicoll RA. SynDIG1 promotes excitatory synaptogenesis independent of AMPA receptor trafficking and biophysical regulation. PLoS One. 2013;8:1–7. doi: 10.1371/journal.pone.0066171.10.1371/journal.pone.0066171PMC368196823785483Matt L, Kirk LM, Chenaux G, Speca DJ, Puhger KR, Pride MC, Qneibi M, Haham T, Plambeck KE, Stern-Bach Y, Silverman JL, Crawley JN, Hell JW, Díaz E. SynDIG4/Prrt1 is required for excitatory synapse development and plasticity underlying cognitive function. Cell Rep. 2018;22:2455–2468. doi: 10.1016/j.celrep.2018.02.026.10.1016/j.celrep.2018.02.026PMC585612629490264Valtorta F, Benfenati F, Zara F, Meldolesi J. PRRT2: from paroxysmal disorders to regulation of synaptic function. Trends Neurosci. 2016;39:668–679. doi: 10.1016/j.tins.2016.08.005.10.1016/j.tins.2016.08.00527624551Valente P, Castroflorio E, Rossi P, Fadda M, Sterlini B, Cervigni RI, Prestigio C, Giovedì S, Onofri F, Mura E, Guarnieri FC, Marte A, Orlando M, Zara F, Fassio A, Valtorta F, Baldelli P, Corradi A, Benfenati F. PRRT2 is a key component of the Ca2+-dependent neurotransmitter release machinery. Cell Rep. 2016;15:117–131. doi: 10.1016/j.celrep.2016.03.005.10.1016/j.celrep.2016.03.005PMC482644127052163Coleman J, Jouannot O, Ramakrishnan SK, Zanetti MN, Wang J, Salpietro V, Houlden H, Rothman JE, Krishnakumar SS. PRRT2 regulates synaptic fusion by directly modulating SNARE complex assembly. Cell Rep. 2018;22:820–831. doi: 10.1016/j.celrep.2017.12.056.10.1016/j.celrep.2017.12.056PMC579245029346777Liu Y-T, Nian F-S, Chou W-J, Tai C-Y, Kwan S-Y, Chen C, Kuo P-W, Lin P-H, Chen C-Y, Huang C-W, Lee Y-C, Soong B-W, Tsai J-W. PRRT2 mutations lead to neuronal dysfunction and neurodevelopmental defects. Oncotarget. 2016;7:39184–39196.PMC512992427172900Li M, Niu F, Zhu X, Wu X, Shen N, Peng X, Liu Y. PRRT2 mutant leads to dysfunction of glutamate signaling. Int J Mol Sci. 2015;16:9134–9151. doi: 10.3390/ijms16059134.10.3390/ijms16059134PMC446358225915028Nedivi E, Hevroni D, Naot D, Israeli D, Citri Y. Numerous candidate plasticity-related genes revealed by differential cDNA cloning. Nature. 1993;363:718–722. doi: 10.1038/363718a0.10.1038/363718a08515813Nedivi E, Wu GY, Cline HT. Promotion of dendritic growth by CPG15, an activity-induced signaling molecule. Science. 1998;281:1863–1866. doi: 10.1126/science.281.5384.1863.10.1126/science.281.5384.1863PMC30880139743502Corriveau RA, Shatz CJ, Nedivi E. Dynamic regulation of cpg15 during activity-dependent synaptic development in the mammalian visual system. J Neurosci. 1999;19:7999–8008. doi: 10.1523/JNEUROSCI.19-18-07999.1999.10.1523/JNEUROSCI.19-18-07999.1999PMC306070510479700Cantallops I, Haas K, Cline HT. Postsynaptic CPG15 promotes synaptic maturation and presynaptic axon arbor elaboration in vivo. Nat Neurosci. 2000;3:1004–1011. doi: 10.1038/79823.10.1038/7982311017173Fujino T, Lee WCA, Nedivi E. Regulation of cpg15 by signaling pathways that mediate synaptic plasticity. Mol Cell Neurosci. 2003;24:538–554. doi: 10.1016/S1044-7431(03)00230-6.10.1016/S1044-7431(03)00230-6PMC306597514664806Shimada T, Yoshida T, Yamagata K. Neuritin mediates activity-dependent axonal branch formation in part via FGF signaling. J Neurosci. 2016;36:4534–4548. doi: 10.1523/JNEUROSCI.1715-15.2016.10.1523/JNEUROSCI.1715-15.2016PMC660182527098696Javaherian A, Cline HT. Coordinated motor neuron axon growth and neuromuscular synaptogenesis are promoted by CPG15 in vivo. Neuron. 2005;45:505–512. doi: 10.1016/j.neuron.2004.12.051.10.1016/j.neuron.2004.12.05115721237Picard N, Leslie JH, Trowbridge SK, Subramanian J, Nedivi E, Fagiolini M. Aberrant development and plasticity of excitatory visual cortical networks in the absence of cpg15. J Neurosci. 2014;34:3517–3522. doi: 10.1523/JNEUROSCI.2955-13.2014.10.1523/JNEUROSCI.2955-13.2014PMC394257124599452Fujino T, Leslie JH, Eavri R, Chen JL, Lin WC, Flanders GH, Borok E, Horvath TL, Nedivi E. CPG15 regulates synapse stability in the developing and adult brain CPG15. Genes Dev. 2011;25:2674–2685. doi: 10.1101/gad.176172.111.10.1101/gad.176172.111PMC324868722190461Yao JJ, Zhao QR, Liu DD, Chow CW, Mei YA. Neuritin up-regulates Kv4.2 α-subunit of potassium channel expression and affects neuronal excitability by regulating the calcium–calcineurin–NFATc4 signaling pathway. J Biol Chem. 2016;291:17369–17381. doi: 10.1074/jbc.M115.708883.10.1074/jbc.M115.708883PMC501613427307045Moreno TA, Bronner-Fraser M. Neural expression of mouse Noelin-1/2 and comparison with other vertebrates. Mech Dev. 2002;119:121–125. doi: 10.1016/S0925-4773(02)00308-8.10.1016/S0925-4773(02)00308-812385760Anholt R. Olfactomedin proteins: central players in development and disease. Front Cell Dev Biol. 2014;26:2–6.PMC420699325364714Barembaum M, Moreno TA, LaBonne C, Sechrist J, Bronner-Fraser M. Noelin-1 is a secreted glycoprotein involved in generation of the neural crest. Nat Cell Biol. 2000;2:219–225. doi: 10.1038/35008643.10.1038/3500864310783240Nakaya N, Lee HS, Takada Y, Tzchori I, Tomarev SI. Zebrafish olfactomedin 1 regulates retinal axon elongation in vivo. J Neurosci. 2008;28:7900–7910. doi: 10.1523/JNEUROSCI.0617-08.2008.10.1523/JNEUROSCI.0617-08.2008PMC269220918667622Nakaya N, Sultana A, Lee HS, Tomarev SI. Olfactomedin 1 interacts with the Nogo A receptor complex to regulate axon growth. J Biol Chem. 2012;287:37171–37184. doi: 10.1074/jbc.M112.389916.10.1074/jbc.M112.389916PMC348131722923615Lee J-A, Anholt RRH, Cole GJ. Olfactomedin-2 mediates development of the anterior central nervous system and head structures in zebrafish. Mech Dev. 2008;125:167–181. doi: 10.1016/j.mod.2007.09.009.10.1016/j.mod.2007.09.009PMC224741318037275Nakaya N, Sultana A, Munasinghe J, Cheng A, Mattson MP, Tomarev SI. Deletion in the N-terminal half of olfactomedin 1 modifies its interaction with synaptic proteins and causes brain dystrophy and abnormal behavior in mice. Exp Neurol. 2013;250:205–218. doi: 10.1016/j.expneurol.2013.09.019.10.1016/j.expneurol.2013.09.019PMC387522724095980Nakaya N, Sultana A, Tomarev SI. Impaired AMPA receptor trafficking by a double knockout of zebrafish olfactomedin1a/b. J Neurochem. 2017;143:635–644. doi: 10.1111/jnc.14231.10.1111/jnc.14231PMC572908228975619Sultana A, Nakaya N, Dong L, Abu-Asab M, Qian H, Tomarev SI. Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice. Exp Neurol. 2014;261:802–811. doi: 10.1016/j.expneurol.2014.09.002.10.1016/j.expneurol.2014.09.002PMC419424025218043Pandya NJ, Seeger C, Babai N, Gonzalez-Lozano MA, Mack V, Lodder JC, Gouwenberg Y, Mansvelder HD, Danielson UH, Li KW, Heine M, Spijker S, Frischknecht R, Smit AB. Noelin1 affects lateral mobility of synaptic AMPA receptors. Cell Rep. 2018;24:1218–1230. doi: 10.1016/j.celrep.2018.06.102.10.1016/j.celrep.2018.06.102PMC608813630067977Koike N, Kassai Y, Kouta Y, Miwa H, Konishi M, Itoh N. Brorin, a novel secreted bone morphogenetic protein antagonist, promotes neurogenesis in mouse neural precursor cells. J Biol Chem. 2007;282:15843–15850. doi: 10.1074/jbc.M701570200.10.1074/jbc.M70157020017400546Miyake A, Mekata Y, Fujibayashi H, Nakanishi K, Konishi M, Itoh N. Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance in the zebra-sh forebrain. PLoS One. 2017;12:1–21.PMC540782228448525Miwa H, Miyake A, Kouta Y, Shimada A, Yamashita Y, Nakayama Y, Yamauchi H, Konishi M, Itoh N. A novel neural-specific BMP antagonist, Brorin-like, of the Chordin family. FEBS Lett. 2009;583:3643–3648. doi: 10.1016/j.febslet.2009.10.044.10.1016/j.febslet.2009.10.04419852960Ohyama Y, Katafuchi M, Almehmadi A, Venkitapathi S, Jaha H, Ehrenman J, Morcos J, Aljamaan R, Mochida Y. Modulation of matrix mineralization by Vwc2-like protein and its novel splicing isoforms. Biochem Biophys Res Commun. 2012;418:12–16. doi: 10.1016/j.bbrc.2011.12.075.10.1016/j.bbrc.2011.12.075PMC327365622209847Popovic M, Rensen-De Leeuw M, Rehmann H. Selectivity of CDC25 homology domain-containing guanine nucleotide exchange factors. J Mol Biol. 2013;425:2782–2794. doi: 10.1016/j.jmb.2013.04.031.10.1016/j.jmb.2013.04.03123659792Uechi Y, Bayarjargal M, Umikawa M, Oshiro M, Takei K, Yamashiro Y, Asato T, Endo S, Misaki R, Taguchi T, Kariya K. Rap2 function requires palmitoylation and recycling endosome localization. Biochem Biophys Res Commun. 2009;378:732–737. doi: 10.1016/j.bbrc.2008.11.107.10.1016/j.bbrc.2008.11.10719061864Zhu Z, Di J, Lu Z, Gao K, Zheng J. Rap2B GTPase: structure, functions, and regulation. Tumor Biol. 2016;37:7085–7093. doi: 10.1007/s13277-016-5033-y.10.1007/s13277-016-5033-y27012552Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell. 2002;110:443–455. doi: 10.1016/S0092-8674(02)00897-8.10.1016/S0092-8674(02)00897-812202034Zhu Y, Pak D, Qin Y, Mccormack SG, Kim MJ, Baumgart JP, Velamoor V, Auberson YP, Osten P, Van Aelst L, Sheng M, Zhu JJ. Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron. 2005;46:905–916. doi: 10.1016/j.neuron.2005.04.037.10.1016/j.neuron.2005.04.03715953419Kielland A, Bochorishvili G, Corson J, Zhang L, Rosin DL, Heggelund P, Zhu JJ. Activity patterns govern synapse-specific AMPA receptor trafficking between deliverable and synaptic pools. Neuron. 2009;62:84–101. doi: 10.1016/j.neuron.2009.03.001.10.1016/j.neuron.2009.03.001PMC268222019376069Hussain NK, Hsin H, Huganir RL, Sheng M. MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and ampa receptor function. J Neurosci. 2010;30:14786–14794. doi: 10.1523/JNEUROSCI.4124-10.2010.10.1523/JNEUROSCI.4124-10.2010PMC307094321048137Zhang L, Zhang P, Wang G, Zhang H, Zhang Y, Yu Y, Zhang M, Xiao J, Crespo P, Hell JW, Lin L, Huganir RL, Zhu JJ. Ras and Rap signal bidirectional synaptic plasticity via distinct subcellular microdomains. Neuron. 2018;98:783–800.e4. doi: 10.1016/j.neuron.2018.03.049.10.1016/j.neuron.2018.03.049PMC619204429706584Stornetta RL, Zhu JJ. Ras and Rap signaling in synaptic plasticity and mental disorders. Neuroscientist. 2011;17:54–78. doi: 10.1177/1073858410365562.10.1177/1073858410365562PMC311950720431046Fu Z, Lee SH, Simonetta A, Hansen J, Sheng M, Pak DTS. Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons. J Neurochem. 2007;100:118–131. doi: 10.1111/j.1471-4159.2006.04195.x.10.1111/j.1471-4159.2006.04195.xPMC1212570617227435Ryu J, Futai K, Feliu M, Weinberg R, Sheng M. Constitutively active Rap2 transgenic mice display fewer dendritic spines, reduced extracellular signal-regulated kinase signaling, enhanced long-term depression, and impaired spatial learning and fear extinction. J Neurosci. 2008;28:8178–8188. doi: 10.1523/JNEUROSCI.1944-08.2008.10.1523/JNEUROSCI.1944-08.2008PMC266513018701680Lee KJ, Lee Y, Rozeboom A, Lee JY, Udagawa N, Hoe HS, Pak DTS. Requirement for Plk2 in orchestrated Ras and Rap signaling, homeostatic structural plasticity, and memory. Neuron. 2011;69:957–973. doi: 10.1016/j.neuron.2011.02.004.10.1016/j.neuron.2011.02.004PMC307382821382555Marrs WR, Blankman JL, Horne EA, Thomazeau A, Lin YH, Coy J, Bodor AL, Muccioli GG, Hu SSJ, Woodruff G, Fung S, Lafourcade M, Alexander JP, Long JZ, Li W, Xu C, Möller T, MacKie K, Manzoni OJ, Cravatt BF, Stella N. The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nat Neurosci. 2010;13:951–957. doi: 10.1038/nn.2601.10.1038/nn.2601PMC297052320657592Wei M, Zhang J, Jia M, Yang C, Pan Y, Li S, Luo Y, Zheng J, Ji J, Chen J, Hu X, Xiong J, Shi Y, Zhang C. α/β-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors. Proc Natl Acad Sci. 2016;113:E2695–E2704. doi: 10.1073/pnas.1524589113.10.1073/pnas.1524589113PMC486848427114538Erlenhardt N, Yu H, Abiraman K, Yamasaki T, Wadiche JI, Tomita S, Bredt DS. Porcupine controls hippocampal AMPAR levels, composition, and synaptic transmission. Cell Rep. 2016;14:782–794. doi: 10.1016/j.celrep.2015.12.078.10.1016/j.celrep.2015.12.078PMC495562726776514Wei M, Jia M, Zhang J, Yu L, Zhao Y, Chen Y, Ma Y, Zhang W, Shi YS, Zhang C. The inhibitory effect of α/β-hydrolase domain-containing 6 (ABHD6) on the surface targeting of GluA2- and GluA3-containing AMPA receptors. Front Mol Neurosci. 2017;10:1–12. doi: 10.3389/fnmol.2017.00055.10.3389/fnmol.2017.00055PMC533349428303090Brechet A, Buchert R, Schwenk J, Boudkkazi S, Zolles G, Siquier-Pernet K, Schaber I, Bildl W, Saadi A, Bole-Feysot C, Nitschke P, Reis A, Sticht H, Al-Sanna’a N, Rolfs A, Kulik A, Schulte U, Colleaux L, Abou Jamra R, Fakler B. AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability. Nat Commun. 2017;8:15910. doi: 10.1038/ncomms15910.10.1038/ncomms15910PMC550089228675162Casals N, Zammit V, Herrero L, Fadó R, Rodríguez-Rodríguez R, Serra D. Carnitine palmitoyltransferase 1C: from cognition to cancer. Prog Lipid Res. 2016;61:134–148. doi: 10.1016/j.plipres.2015.11.004.10.1016/j.plipres.2015.11.00426708865Carrasco P, Sahún I, McDonald J, Ramírez S, Jacas J, Gratacós E, Sierra AY, Serra D, Herrero L, Acker-Palmer A, Hegardt FG, Dierssen M, Casals N. Ceramide levels regulated by carnitine palmitoyltransferase 1C control dendritic spine maturation and cognition. J Biol Chem. 2012;287:21224–21232. doi: 10.1074/jbc.M111.337493.10.1074/jbc.M111.337493PMC337554422539351Passafaro M, Nakagawa T, Sala C, Sheng M. Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2. Nature. 2003;424:677–681. doi: 10.1038/nature01781.10.1038/nature0178112904794Gratacòs-Batlle E, Yefimenko N, Cascos-Garcia H, Soto D. AMPAR interacting protein CPT1C enhances surface expression of GluA1-containing receptors. Front Cell Neurosci. 2015;8:1–17.PMC431369925698923Fadó R, Soto D, Miñano-Molina AJ, Pozo M, Carrasco P, Yefimenko N, Rodríguez-Álvarez J, Casals N. Novel regulation of the synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (ampa) receptor subunit glua1 by carnitine palmitoyltransferase 1C (CPT1C) in the Hippocampus. J Biol Chem. 2015;290:25548–25560. doi: 10.1074/jbc.M115.681064.10.1074/jbc.M115.681064PMC464620026338711Yang G, Zhou X, Zhu J, Liu R, Zhang S, Coquinco A, Chen Y, Wen Y, Kojic L, Jia W, Cynader MS. JNK3 couples the neuronal stress response to inhibition of secretory trafficking. Sci Signal. 2013;6:1–11.23838184Madeo M, Stewart M, Sun Y, Sahir N, Wiethoff S, Chandrasekar I, Yarrow A, Rosenfeld JA, Yang Y, Cordeiro D, McCormick EM, Muraresku CC, Jepperson TN, McBeth LJ, Seidahmed MZ, El Khashab HY, Hamad M, Azzedine H, Clark K, Corrochano S, Wells S, Elting MW, Weiss MM, Burn S, Myers A, Landsverk M, Crotwell PL, Waisfisz Q, Wolf NI, Nolan PM, Padilla-Lopez S, Houlden H, Lifton R, Mane S, Singh BB, Falk MJ, Mercimek-Mahmutoglu S, Bilguvar K, Salih MA, Acevedo-Arozena A, Kruer MC. Loss-of-function mutations in FRRS1L lead to an epileptic-dyskinetic encephalopathy. Am J Hum Genet. 2016;98:1249–1255. doi: 10.1016/j.ajhg.2016.04.008.10.1016/j.ajhg.2016.04.008PMC490817827236917Han W, Wang H, Li J, Zhang S, Lu W. Ferric chelate reductase 1 like protein (FRRS1L) associates with dynein vesicles and regulates glutamatergic synaptic transmission. Front Mol Neurosci. 2017;10:1–15.PMC572712129276473Kadowaki T, Wilder E, Klingensmith J, Zachary K, Perrimon N. The segment polarity gene porcupine encodes a putative multitransmembrane protein involved in Wingless processing. Genes Dev. 1996;10:3116–3128. doi: 10.1101/gad.10.24.3116.10.1101/gad.10.24.31168985181Tanaka K, Okabayashi K, Asashima M, Perrimon N, Kadowaki T. The evolutionarily conserved porcupine family is involved in the processing of the Wnt family. Eur J Biochem. 2000;267:4300–4311. doi: 10.1046/j.1432-1033.2000.01478.x.10.1046/j.1432-1033.2000.01478.x10866835Li YH, Zhang N, Wang YN, Shen Y, Wang Y. Multiple faces of protein interacting with C kinase 1 (PICK1): structure, function, and diseases. Neurochem Int. 2016;98:115–121. doi: 10.1016/j.neuint.2016.03.001.10.1016/j.neuint.2016.03.00126970394Coley AA, Gao WJ. PSD95: a synaptic protein implicated in schizophrenia or autism? Prog Neuro-Psychopharmacol Biol Psychiatry. 2018;82:187–194. doi: 10.1016/j.pnpbp.2017.11.016.10.1016/j.pnpbp.2017.11.016PMC580104729169997Han J, Wu P, Wang F, Chen J. S-palmitoylation regulates AMPA receptors trafficking and function: a novel insight into synaptic regulation and therapeutics. Acta Pharm Sin B. 2015;5:1–7. doi: 10.1016/j.apsb.2014.12.002.10.1016/j.apsb.2014.12.002PMC462913826579419Widagdo J, Guntupalli S, Jang SE, Anggono V. Regulation of AMPA receptor trafficking by protein ubiquitination. Front Mol Neurosci. 2017;10:1–10. doi: 10.3389/fnmol.2017.00347.10.3389/fnmol.2017.00347PMC566275529123470