Cited by 278Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersTreatment of Major Depression

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

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Kim, Myung Jong, Futai, Kensuke, Jo, Jihoon, Hayashi, Yasunori, Cho, Kwangwook, Sheng, Morgan·2007·Neuron

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.

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Crossref · 10.1016/j.neuron.2007.09.007

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Authors
Kim, M. J., Futai, K., Jo, J., Hayashi, Y., Cho, K., & Sheng, M.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of Bristol (GB)
Corresponding author
Sheng, Morgan
Venue
Neuron
Publisher
Elsevier BV
Published
2007-11
Volume
56
Issue
3
Pages
488-502
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2003931473
Cited by
278
References
35
Citations by year
2026: 12 · 2025: 11 · 2024: 9 · 2023: 9 · 2022: 18 · 2021: 15 · 2020: 17 · 2019: 15 · 2018: 16 · 2017: 19 · 2016: 17 · 2015: 12 · 2014: 15 · 2013: 19 · 2012: 13
FWCI
5.04
Type
journal article
Language
en
Update notices
erratum (2008-01-24)
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Bristol Research (University of Bristol) (submittedVersion)
  • Explore Bristol Research (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • Biotechnology and Biological Sciences Research Council (BB/D013232/2)
  • RIKEN
  • National Institute of Mental Health (R01MH076936, MH076936)
  • National Institute on Drug Abuse (DA017310)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
PSD-95, postsynaptic density, excitatory postsynaptic currents, Rac1, JNK1, synaptic plasticity, long-term depression, NMDA, AMPA receptor internalization, scaffold proteins
MeSH terms
Disks Large Homolog 4 Protein, Animals, Animals, Newborn, Cells, Cultured, Hippocampus, Membrane Proteins, Mutation, Synaptic Transmission, Organ Culture Techniques, Phosphorylation, Serine, Synaptic Membranes, Signal Transduction, N-Methylaspartate, Receptors, AMPA, Excitatory Amino Acid Agonists, Excitatory Postsynaptic Potentials, rac1 GTP-Binding Protein, Long-Term Synaptic Depression, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Rats

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