Heterogeneity in the molecular composition of excitatory postsynaptic sites during development of hippocampal neurons in culture

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dc.contributor.authorRao, Ako
dc.contributor.authorKim, Eunjoonko
dc.contributor.authorSheng, Mko
dc.contributor.authorCraig, AMko
dc.date.accessioned2013-03-03T06:25:35Z-
dc.date.available2013-03-03T06:25:35Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued1998-02-
dc.identifier.citationJOURNAL OF NEUROSCIENCE, v.18, no.4, pp.1217 - 1229-
dc.identifier.issn0270-6474-
dc.identifier.urihttp://hdl.handle.net/10203/77627-
dc.description.abstractTo determine their roles in the assembly of glutamatergic postsynaptic sites, we studied the distributions of NMDA-and AMPA-type glutamate receptors; the NMDA receptor-interacting proteins alpha-actinin-2, PSD-95, and chapsyn; and the PSD-95-associated protein GKAP during the development of hippocampal neurons in culture. NMDA receptors first formed nonsynaptic proximal dendrite shaft clusters within 2-5 d. AMPA receptors were diffuse at this stage and began to cluster on spines at 9-10 d. NMDA receptor clusters remained partially nonsynaptic and mainly distinct from AMPA receptor clusters until after 3 weeks in culture, when the two began to colocalize at spiny synaptic sites. Thus, the localization of NMDA and AMPA receptors must be regulated by different mechanisms. alpha-Actinin-2 colocalized with the NMDA receptor only at spiny synaptic clusters, but not at shaft nonsynaptic or synaptic clusters, suggesting a modulatory role in the anchoring of NMDA receptor at spines. PSD-95, chapsyn, and GKAP were present at some, but not all, nonsynaptic NMDA receptor clusters during the first 2 weeks, indicating that none is essential for NMDA receptor cluster formation. When NMDA receptor clusters became synaptic, PSD-95 and GKAP were always present, consistent with an essential function in synaptic localization of NMDA receptors. Furthermore, PSD-95 and GKAP clustered opposite presynaptic terminals several days before either NMDA or AMPA receptors clustered at these presumptive postsynaptic sites. These results suggest that synapse development proceeds by formation of a postsynaptic scaffold containing PSD-95 and GKAP in concert with presynaptic vesicle clustering, followed by regulated attachment of glutamate receptor subtypes to this scaffold.-
dc.languageEnglish-
dc.publisherSOC NEUROSCIENCE-
dc.subjectNMDA RECEPTOR SUBUNITS-
dc.subjectRAT-BRAIN-
dc.subjectGLUTAMATE RECEPTORS-
dc.subjectMONKEY HIPPOCAMPUS-
dc.subjectGUANYLATE KINASES-
dc.subjectENDOCRINE-CELLS-
dc.subjectSILENT SYNAPSES-
dc.subjectVISUAL-CORTEX-
dc.subjectPSD-95 FAMILY-
dc.subjectNR1 SUBUNIT-
dc.titleHeterogeneity in the molecular composition of excitatory postsynaptic sites during development of hippocampal neurons in culture-
dc.typeArticle-
dc.identifier.wosid000071825800004-
dc.identifier.scopusid2-s2.0-0032520191-
dc.type.rimsART-
dc.citation.volume18-
dc.citation.issue4-
dc.citation.beginningpage1217-
dc.citation.endingpage1229-
dc.citation.publicationnameJOURNAL OF NEUROSCIENCE-
dc.contributor.localauthorKim, Eunjoon-
dc.contributor.nonIdAuthorRao, A-
dc.contributor.nonIdAuthorSheng, M-
dc.contributor.nonIdAuthorCraig, AM-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorNMDA receptor-
dc.subject.keywordAuthorAMPA receptor-
dc.subject.keywordAuthorPSD-95-
dc.subject.keywordAuthorPSD-93-
dc.subject.keywordAuthorPDZ domain-
dc.subject.keywordAuthoralpha-actinin-2-
dc.subject.keywordAuthorchapsyn-
dc.subject.keywordAuthorGKAP-
dc.subject.keywordAuthorpostsynaptic membrane-
dc.subject.keywordAuthordendritic spines-
dc.subject.keywordPlusNMDA RECEPTOR SUBUNITS-
dc.subject.keywordPlusRAT-BRAIN-
dc.subject.keywordPlusGLUTAMATE RECEPTORS-
dc.subject.keywordPlusMONKEY HIPPOCAMPUS-
dc.subject.keywordPlusGUANYLATE KINASES-
dc.subject.keywordPlusENDOCRINE-CELLS-
dc.subject.keywordPlusSILENT SYNAPSES-
dc.subject.keywordPlusVISUAL-CORTEX-
dc.subject.keywordPlusPSD-95 FAMILY-
dc.subject.keywordPlusNR1 SUBUNIT-
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