RGD Reference Report - Phosphorylation of threonine-19 of PSD-95 by GSK-3ß is required for PSD-95 mobilization and long-term depression. - Rat Genome Database

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Phosphorylation of threonine-19 of PSD-95 by GSK-3ß is required for PSD-95 mobilization and long-term depression.

Authors: Nelson, Christopher D  Kim, Myung Jong  Hsin, Honor  Chen, Yelin  Sheng, Morgan 
Citation: Nelson CD, etal., J Neurosci. 2013 Jul 17;33(29):12122-35. doi: 10.1523/JNEUROSCI.0131-13.2013.
RGD ID: 13702314
Pubmed: (View Article at PubMed) PMID:23864697
DOI: Full-text: DOI:10.1523/JNEUROSCI.0131-13.2013

Activity of glycogen synthase kinase-3ß (GSK-3ß) 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-3ß. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3ß. 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-3ß destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD.

Annotation

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Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Gsk3b  (glycogen synthase kinase 3 beta)


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