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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Yukihiro Takayasu
  • Alma Rodenas-Ruano
  • Ana V. Paternain
  • Juan Lerma
  • Michael V. L. Bennett
  • R. Suzanne Zukin

Detail(s)

Original languageEnglish
Pages (from-to)242-254
Journal / PublicationJournal of Neuroscience
Volume30
Issue number1
Publication statusPublished - 6 Jan 2010
Externally publishedYes

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©2010 the authors.

Citation Format(s)

SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking. / Lau, C. Geoffrey; Takayasu, Yukihiro; Rodenas-Ruano, Alma; Paternain, Ana V.; Lerma, Juan; Bennett, Michael V. L.; Suzanne Zukin, R.

In: Journal of Neuroscience, Vol. 30, No. 1, 06.01.2010, p. 242-254.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal