SNAP-25 Is a Target of Protein Kinase C Phosphorylation Critical to NMDA Receptor Trafficking

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 prote...

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Bibliographic Details
Published in:The Journal of neuroscience 2010-01, Vol.30 (1), p.242-254
Main Authors: Lau, C. Geoffrey, Takayasu, Yukihiro, Rodenas-Ruano, Alma, Paternain, Ana V, Lerma, Juan, Bennett, Michael V. L, Zukin, R. Suzanne
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Line
Cells, Cultured
Female
Gene Targeting
Humans
Mice
Mice, Mutant Strains
Molecular Sequence Data
Phosphorylation
Protein Binding - physiology
Protein Kinase C - genetics
Protein Kinase C - metabolism
Protein Transport - physiology
Rats
Receptors, N-Methyl-D-Aspartate - genetics
Receptors, N-Methyl-D-Aspartate - metabolism
Synaptosomal-Associated Protein 25 - genetics
Synaptosomal-Associated Protein 25 - metabolism
Xenopus laevis
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.4933-08.2010