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1529-24012292002May01The Journal of neuroscience : the official journal of the Society for NeuroscienceJ NeurosciDifferential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters.349335033493-503Long-term changes in excitatory synapse strength are thought to reflect changes in synaptic abundance of AMPA receptors mediated by receptor trafficking. AMPA receptor-binding protein (ABP) and glutamate receptor-interacting protein (GRIP) are two similar PDZ (postsynaptic density 95/Discs large/zona occludens 1) proteins that interact with glutamate receptors 2 and 3 (GluR2 and GluR3) subunits. Both proteins have proposed roles during long-term potentiation and long-term depression in the delivery and anchorage of AMPA receptors at synapses. Here we report a variant of ABP-L (seven PDZ form of ABP) called pABP-L that is palmitoylated at a cysteine residue at position 11 within a novel 18 amino acid N-terminal leader sequence encoded through differential splicing. In cultured hippocampal neurons, nonpalmitoylated ABP-L localizes with internal GluR2 pools expressed from a Sindbis virus vector, whereas pABP-L is membrane targeted and associates with surface-localized GluR2 receptors at the plasma membrane in spines. Mutation of Cys-11 to alanine blocks the palmitoylation of pABP-L and targets the protein to intracellular clusters, confirming that targeting the protein to spines is dependent on palmitoylation. Non-palmitoylated GRIP is primarily intracellular, but a chimera with the pABP-L N-terminal palmitoylation sequence linked to the body of the GRIP protein is targeted to spines. We suggest that pABP-L and ABP-L provide, respectively, synaptic and intracellular sites for the anchorage of AMPA receptors during receptor trafficking to and from the synapse.DeSouzaSunitaSHoward Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA.FuJieJStatesBradley ABAZiffEdward BEBengR01 AG013620AGNIA NIH HHSUnited StatesR37 AG013620AGNIA NIH HHSUnited StatesAG13620AGNIA NIH HHSUnited StatesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.
United StatesJ Neurosci81021400270-64740Adaptor Proteins, Signal Transducing0Carrier Proteins0GRIP2 protein, human0Grip2 protein, rat0Intercellular Signaling Peptides and Proteins0Macromolecular Substances0Nerve Tissue Proteins0Nuclear Receptor Coactivator 20Palmitic Acids0Protein Isoforms0RNA, Messenger0Receptors, AMPA0Recombinant Fusion Proteins0Transcription FactorsP6W5IXV8V9glutamate receptor ionotropic, AMPA 2IMAdaptor Proteins, Signal TransducingAlternative SplicingAmino Acid SequenceAmino Acid SubstitutionAnimalsCarrier ProteinsgeneticsmetabolismCell MembranemetabolismCell Surface ExtensionsmetabolismCells, CulturedCloning, MolecularGenes, ReporterHumansIntercellular Signaling Peptides and ProteinsIntracellular FluidmetabolismKidneycytologymetabolismMacromolecular SubstancesMaleMolecular Sequence DataMutagenesis, Site-DirectedNerve Tissue ProteinsgeneticsmetabolismNeuronscytologymetabolismNuclear Receptor Coactivator 2Organ SpecificityPalmitic AcidsmetabolismProtein IsoformsgeneticsmetabolismProtein TransportphysiologyRNA, MessengermetabolismRatsRats, Sprague-DawleyReceptors, AMPAgeneticsmetabolismRecombinant Fusion ProteinsgeneticsmetabolismTranscription FactorsgeneticsmetabolismTransfection2002430100200252210120024301002002111ppublish11978826PMC675837822/9/349310.1523/JNEUROSCI.22-09-03493.2002Alland L, Peseckis SM, Atherton RE, Berthiaume L, Resh MD. 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