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- Title
SNAP-25 Is a Target of Protein Kinase C Phosphorylation Critical to NMDA Receptor Trafficking.
- Authors
Lau, C. Geoffrey; Takayasu, Yukihiro; Rodenas-Ruano, Alma; Paternain, Ana V.; Lerma, Juan; Bennett, Michael V. L.; Zukin, R. Suzanne
- 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 NMDAEPSCs 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.
- Subjects
PROTEIN kinases; PHOSPHORYLATION; METHYL aspartate; EXOCYTOSIS; HIPPOCAMPUS physiology; BLOCKING antibodies; IMMUNOSUPPRESSION; NEUROPLASTICITY
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 1, p242
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4933-08.2010