SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking
Open accessAbstract
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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SNAP-25 has recently been shown to facilitate the removal of kainate receptors (KARs) from the membrane surface.
“Moreover, SNAP-25 has recently been shown to facilitate the removal of kainate receptors (KARs), which are implicated in epileptogenesis, from the membrane surface (83, 90 -95).”
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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)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-01-06
- Volume
- 30
- Issue
- 1
- Pages
- 242-254
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3397691
- 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
- hybrid
- doi.org
- Licence
- 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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