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<PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Manual"><PMID Version="1">28904092</PMID><DateCompleted><Year>2017</Year><Month>10</Month><Day>23</Day></DateCompleted><DateRevised><Year>2026</Year><Month>01</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1529-2401</ISSN><JournalIssue CitedMedium="Internet"><Volume>37</Volume><Issue>41</Issue><PubDate><Year>2017</Year><Month>Oct</Month><Day>11</Day></PubDate></JournalIssue><Title>The Journal of neuroscience : the official journal of the Society for Neuroscience</Title><ISOAbbreviation>J Neurosci</ISOAbbreviation></Journal><ArticleTitle>MAP1B Light Chain Modulates Synaptic Transmission via AMPA Receptor Intracellular Trapping.</ArticleTitle><Pagination><StartPage>9945</StartPage><EndPage>9963</EndPage><MedlinePgn>9945-9963</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1523/JNEUROSCI.0505-17.2017</ELocationID><Abstract><AbstractText>The regulated transport of AMPA-type glutamate receptors (AMPARs) to the synaptic membrane is a key mechanism to determine the strength of excitatory synaptic transmission in the brain. In this work, we uncovered a new role for the microtubule-associated protein MAP1B in modulating access of AMPARs to the postsynaptic membrane. Using mice and rats of either sex, we show that MAP1B light chain (LC) accumulates in the somatodendritic compartment of hippocampal neurons, where it forms immobile complexes on microtubules that limit vesicular transport. These complexes restrict AMPAR dendritic mobility, leading to the intracellular trapping of receptors and impairing their access to the dendritic surface and spines. Accordingly, increasing MAP1B-LC expression depresses AMPAR-mediated synaptic transmission. This effect is specific for the GluA2 subunit of the AMPAR and requires glutamate receptor interacting protein 1 (GRIP1) interaction with MAP1B-LC. Therefore, MAP1B-LC represents an alternative link between GRIP1-AMPARs and microtubules that does not result in productive transport, but rather limits AMPAR availability for synaptic insertion, with a direct impact on synaptic transmission.<b>SIGNIFICANCE STATEMENT</b> The ability of neurons to modify their synaptic connections, known as synaptic plasticity, is accepted as the cellular basis for learning and memory. One mechanism for synaptic plasticity is the regulated addition and removal of AMPA-type glutamate receptors (AMPARs) at excitatory synapses. In this study, we found that a microtubule-associated protein, MAP1B light chain (MAP1B-LC), participates in this process. MAP1B-LC forms immobile complexes along dendrites. These complexes limit intracellular vesicular trafficking and trap AMPARs inside the dendritic shaft. In this manner, MAP1B restricts the access of AMPARs to dendritic spines and the postsynaptic membrane, contributing to downregulating synaptic transmission.</AbstractText><CopyrightInformation>Copyright &#xa9; 2017 the authors 0270-6474/17/379945-19$15.00/0.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Palenzuela</LastName><ForeName>Roc&#xed;o</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Neurobiology, Centro de Biolog&#xed;a Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient&#xed;ficas-Universidad Aut&#xf3;noma de Madrid), Madrid 28049, Spain, and.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarc&#xf3;n, Madrid 28223, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guti&#xe9;rrez</LastName><ForeName>Yolanda</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurobiology, Centro de Biolog&#xed;a Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient&#xed;ficas-Universidad Aut&#xf3;noma de Madrid), Madrid 28049, Spain, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Draffin</LastName><ForeName>Jonathan E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Department of Neurobiology, Centro de Biolog&#xed;a Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient&#xed;ficas-Universidad Aut&#xf3;noma de Madrid), Madrid 28049, Spain, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lario</LastName><ForeName>Argentina</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Neurobiology, Centro de Biolog&#xed;a Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient&#xed;ficas-Universidad Aut&#xf3;noma de Madrid), Madrid 28049, Spain, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benoist</LastName><ForeName>Marion</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neurobiology, Centro de Biolog&#xed;a Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient&#xed;ficas-Universidad Aut&#xf3;noma de Madrid), Madrid 28049, Spain, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Esteban</LastName><ForeName>Jos&#xe9; A</ForeName><Initials>JA</Initials><Identifier Source="ORCID">0000-0002-3759-3300</Identifier><AffiliationInfo><Affiliation>Department of Neurobiology, Centro de Biolog&#xed;a Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient&#xed;ficas-Universidad Aut&#xf3;noma de Madrid), Madrid 28049, Spain, and jaesteban@cbm.csic.es.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>U24 NS050606</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>09</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Neurosci</MedlineTA><NlmUniqueID>8102140</NlmUniqueID><ISSNLinking>0270-6474</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D048868">Adaptor Proteins, Signal Transducing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008869">Microtubule-Associated Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009419">Nerve Tissue Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018091">Receptors, AMPA</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C491309">Grip1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C085284">microtubule-associated protein 1B</NameOfSubstance></Chemical><Chemical><RegistryNumber>P6W5IXV8V9</RegistryNumber><NameOfSubstance UI="C104722">glutamate receptor ionotropic, AMPA 2</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D048868" MajorTopicYN="N">Adaptor Proteins, Signal Transducing</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003712" MajorTopicYN="N">Dendrites</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049229" MajorTopicYN="N">Dendritic Spines</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006624" MajorTopicYN="N">Hippocampus</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008869" MajorTopicYN="N">Microtubule-Associated Proteins</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009419" MajorTopicYN="N">Nerve Tissue Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009474" MajorTopicYN="N">Neurons</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018091" MajorTopicYN="N">Receptors, AMPA</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013569" MajorTopicYN="N">Synapses</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009435" MajorTopicYN="N">Synaptic Transmission</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">GRIP1</Keyword><Keyword MajorTopicYN="N">GluA1</Keyword><Keyword MajorTopicYN="N">GluA2</Keyword><Keyword MajorTopicYN="N">cytoskeleton</Keyword><Keyword MajorTopicYN="N">hippocampus</Keyword><Keyword MajorTopicYN="N">spine</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>2</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2017</Year><Month>8</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>8</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>9</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>10</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>9</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2018</Year><Month>4</Month><Day>11</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28904092</ArticleId><ArticleId IdType="pmc">PMC6596595</ArticleId><ArticleId IdType="doi">10.1523/JNEUROSCI.0505-17.2017</ArticleId><ArticleId 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