dc.contributor.author | Nelson, Christopher D. | |
dc.contributor.author | Kim, Myung Jong | |
dc.contributor.author | Hsin, Honor | |
dc.contributor.author | Chen, Yelin | |
dc.contributor.author | Sheng, Morgan | |
dc.date.accessioned | 2014-09-02T15:19:23Z | |
dc.date.available | 2014-09-02T15:19:23Z | |
dc.date.issued | 2013-07 | |
dc.date.submitted | 2013-05 | |
dc.identifier.issn | 0270-6474 | |
dc.identifier.issn | 1529-2401 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/89128 | |
dc.description.abstract | Activity 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.iso | en_US | |
dc.publisher | Society for Neuroscience | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1523/jneurosci.0131-13.2013 | en_US |
dc.rights | Article 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.source | Society for Neuroscience | en_US |
dc.title | Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Nelson, 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.department | Picower Institute for Learning and Memory | en_US |
dc.contributor.mitauthor | Nelson, Christopher D. | en_US |
dc.contributor.mitauthor | Kim, Myung Jong | en_US |
dc.contributor.mitauthor | Hsin, Honor | en_US |
dc.contributor.mitauthor | Chen, Yelin | en_US |
dc.contributor.mitauthor | Sheng, Morgan | en_US |
dc.relation.journal | Journal of Neuroscience | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Nelson, C. D.; Kim, M. J.; Hsin, H.; Chen, Y.; Sheng, M. | en_US |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |