TY - JOUR
T1 - SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking
AU - Lau, C. Geoffrey
AU - Takayasu, Yukihiro
AU - Rodenas-Ruano, Alma
AU - Paternain, Ana V.
AU - Lerma, Juan
AU - Bennett, Michael V.L.
AU - Suzanne Zukin, R.
PY - 2010/1/6
Y1 - 2010/1/6
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=74849097142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74849097142&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4933-08.2010
DO - 10.1523/JNEUROSCI.4933-08.2010
M3 - Article
C2 - 20053906
AN - SCOPUS:74849097142
VL - 30
SP - 242
EP - 254
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 1
ER -