Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.69 (
botulinum neurotoxin
)
1,901
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking. 2005 6
