Synaptic Accumulation of PSD-95 and Synaptic Function Regulated by Phosphorylation of Serine-295 of PSD-95

Myung Jong Kim, Kensuke Futai, Jihoon Jo, Yasunori Hayashi, Kwangwook Cho, Morgan Sheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

The scaffold protein PSD-95 promotes the maturation and strengthening of excitatory synapses, functions that require proper localization of PSD-95 in the postsynaptic density (PSD). Here we report that phosphorylation of ser-295 enhances the synaptic accumulation of PSD-95 and the ability of PSD-95 to recruit surface AMPA receptors and potentiate excitatory postsynaptic currents. We present evidence that a Rac1-JNK1 signaling pathway mediates ser-295 phosphorylation and regulates synaptic content of PSD-95. Ser-295 phosphorylation is suppressed by chronic elevation, and increased by chronic silencing, of synaptic activity. Rapid dephosphorylation of ser-295 occurs in response to NMDA treatment that causes chemical long-term depression (LTD). Overexpression of a phosphomimicking mutant (S295D) of PSD-95 inhibited NMDA-induced AMPA receptor internalization and blocked the induction of LTD. The data suggest that synaptic strength can be regulated by phosphorylation-dephosphorylation of ser-295 of PSD-95 and that synaptic depression requires the dephosphorylation of ser-295.

Original languageEnglish (US)
Pages (from-to)488-502
Number of pages15
JournalNeuron
Volume56
Issue number3
DOIs
StatePublished - Nov 8 2007

Keywords

  • CELLBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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