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

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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

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Synaptosomal-Associated Protein 25
N-Methyl-D-Aspartate Receptors
Protein Kinase C
Phosphorylation
SNARE Proteins
Peptides
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neuronal Plasticity
Blocking Antibodies
Exocytosis
N-Methylaspartate
RNA Interference
Synapses
Serine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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.; Zukin, R. Suzanne.

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

Research output: Contribution to journalArticle

Lau, C. Geoffrey ; Takayasu, Yukihiro ; Rodenas-Ruano, Alma ; Paternain, Ana V. ; Lerma, Juan ; Bennett, Michael V. L. ; Zukin, R. Suzanne. / SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 1. pp. 242-254.
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AU - Lerma, Juan

AU - Bennett, Michael V. L.

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