Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression
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Author(s)
Nelson, Christopher D.
Kim, Myung Jong
Hsin, Honor
Chen, Yelin
Sheng, Morgan
Date Issued
July 2013
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
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.
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Final published version
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.
MIT Department
Picower Institute for Learning and Memory
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DOI of Published Version
https://doi.org/10.1523/jneurosci.0131-13.2013
