Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression
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 threoni...
| Principais autores: | , , , , |
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| Outros Autores: | |
| Formato: | Artigo |
| Idioma: | en_US |
| Publicado em: |
Society for Neuroscience
2014
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| Acesso em linha: | http://hdl.handle.net/1721.1/89128 |
| _version_ | 1826207288086495232 |
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| author | Nelson, Christopher D. Kim, Myung Jong Hsin, Honor Chen, Yelin Sheng, Morgan |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Nelson, Christopher D. Kim, Myung Jong Hsin, Honor Chen, Yelin Sheng, Morgan |
| author_sort | Nelson, Christopher D. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:46:59Z |
| format | Article |
| id | mit-1721.1/89128 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:46:59Z |
| publishDate | 2014 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/891282022-10-01T17:05:44Z Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression Nelson, Christopher D. Kim, Myung Jong Hsin, Honor Chen, Yelin Sheng, Morgan Picower Institute for Learning and Memory Nelson, Christopher D. Kim, Myung Jong Hsin, Honor Chen, Yelin Sheng, Morgan 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. 2014-09-02T15:19:23Z 2014-09-02T15:19:23Z 2013-07 2013-05 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/89128 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 http://dx.doi.org/10.1523/jneurosci.0131-13.2013 Journal of Neuroscience 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. application/pdf Society for Neuroscience Society for Neuroscience |
| spellingShingle | Nelson, Christopher D. Kim, Myung Jong Hsin, Honor Chen, Yelin Sheng, Morgan Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression |
| title | Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression |
| title_full | Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression |
| title_fullStr | Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression |
| title_full_unstemmed | Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression |
| title_short | Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression |
| title_sort | phosphorylation of threonine 19 of psd 95 by gsk 3β is required for psd 95 mobilization and long term depression |
| url | http://hdl.handle.net/1721.1/89128 |
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