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dc.contributor.authorNelson, Christopher D.
dc.contributor.authorKim, Myung Jong
dc.contributor.authorHsin, Honor
dc.contributor.authorChen, Yelin
dc.contributor.authorSheng, Morgan
dc.date.accessioned2014-09-02T15:19:23Z
dc.date.available2014-09-02T15:19:23Z
dc.date.issued2013-07
dc.date.submitted2013-05
dc.identifier.issn0270-6474
dc.identifier.issn1529-2401
dc.identifier.urihttp://hdl.handle.net/1721.1/89128
dc.description.abstractActivity of glycogen synthase kinase-3β (GSK-3β) is required for long-term depression (LTD) via molecular mechanisms that are incompletely understood. Here, we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD) that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK-3β. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3β. In organotypic rat hippocampal slices, we find that a nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs AMPA receptor internalization and the induction of LTD. These data indicate that phosphorylation on T19 by GSK-3β destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD.en_US
dc.language.isoen_US
dc.publisherSociety for Neuroscienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1523/jneurosci.0131-13.2013en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceSociety for Neuroscienceen_US
dc.titlePhosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depressionen_US
dc.typeArticleen_US
dc.identifier.citationNelson, C. D., M. J. Kim, H. Hsin, Y. Chen, and M. Sheng. “Phosphorylation of Threonine-19 of PSD-95 by GSK-3  Is Required for PSD-95 Mobilization and Long-Term Depression.” Journal of Neuroscience 33, no. 29 (July 17, 2013): 12122–12135.en_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorNelson, Christopher D.en_US
dc.contributor.mitauthorKim, Myung Jongen_US
dc.contributor.mitauthorHsin, Honoren_US
dc.contributor.mitauthorChen, Yelinen_US
dc.contributor.mitauthorSheng, Morganen_US
dc.relation.journalJournal of Neuroscienceen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsNelson, C. D.; Kim, M. J.; Hsin, H.; Chen, Y.; Sheng, M.en_US
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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