Cited by 120Neuroscience and Neuropharmacology ResearchCellular transport and secretionReceptor Mechanisms and Signaling

SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking

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Lau, C. Geoffrey, Takayasu, Yukihiro, Rodenas-Ruano, Alma, Paternain, Ana V., Lerma, Juan, Bennett, Michael V. L., Zukin, R. Suzanne·2010·The Journal of Neuroscience

Abstract

Protein kinase C (PKC) enhances NMDA receptor (NMDAR)-mediated currents and promotes NMDAR delivery to the cell surface via SNARE-dependent exocytosis. Although the mechanisms of PKC potentiation are established, the molecular target of PKC is unclear. Here we show that synaptosomal-associated protein of 25 kDa (SNAP-25), a SNARE protein, is functionally relevant to PKC-dependent NMDAR insertion, and identify serine residue-187 as the molecular target of PKC phosphorylation. Constitutively active PKC delivered via the patch pipette potentiated NMDA (but not AMPA) whole-cell currents in hippocampal neurons. Expression of RNAi targeting SNAP-25 or mutant SNAP-25(S187A) and/or acute disruption of the SNARE complex by treatment with BoNT A, BoNT B or SNAP-25 C-terminal blocking peptide abolished NMDAR potentiation. A SNAP-25 peptide and function-blocking antibody suppressed PKC potentiation of NMDA EPSCs at mossy fiber-CA3 synapses. These findings identify SNAP-25 as the target of PKC phosphorylation critical to PKC-dependent incorporation of synaptic NMDARs and document a postsynaptic action of this major SNARE protein relevant to synaptic plasticity.

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Crossref · 10.1523/jneurosci.4933-08.2010

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Authors
Lau, C. G., Takayasu, Y., Rodenas-Ruano, A., Paternain, A. V., Lerma, J., Bennett, M. V. L., & Zukin, R. S.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Universitat de Miguel Hernández d'Elx (ES)
Venue
The Journal of Neuroscience
Published
2010-01-06
Volume
30
Issue
1
Pages
242-254
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2034272820
Cited by
120
References
59
Citations by year
2025: 3 · 2024: 4 · 2023: 11 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 13 · 2014: 12 · 2013: 11 · 2012: 11
FWCI
4.53
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS-20752, R01NS020752, NS45287, R01NS045287)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
SNAP-25, protein kinase C, NMDA receptor trafficking, SNARE complex, synaptic potentiation, AMPA receptors, mossy fiber-CA3 synapses, postsynaptic plasticity, hippocampal neurons, exocytosis
MeSH terms
Amino Acid Sequence, Animals, Cell Line, Cells, Cultured, Female, Humans, Mice, Mutant Strains, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Kinase C, Xenopus laevis, Receptors, N-Methyl-D-Aspartate, Gene Targeting, Protein Transport, Synaptosomal-Associated Protein 25, Mice, Rats

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