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

C. Geoffrey Lau, Yukihiro Takayasu, Alma Rodenas-Ruano, Ana V. Paternain, Juan Lerma, Michael V.L. Bennett, R. Suzanne Zukin

Research output: Contribution to journalArticle

80 Scopus citations

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 ofNMDAEPSCs 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. Copyright

Original languageEnglish (US)
Pages (from-to)242-254
Number of pages13
JournalJournal of Neuroscience
Volume30
Issue number1
DOIs
StatePublished - Jan 6 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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