Activity-dependent changes in partial VAMP complexes during neurotransmitter release.
The temporal sequence of SNARE protein interactions that cause exocytosis is unknown. Blockade of synaptic neurotransmitter release through cleavage of VAMP/synaptobrevin by tetanus toxin light chain (TeNT-LC) was accelerated by nerve stimulation. Botulinum/B neurotoxin light chain (BoNT/B-LC), which cleaves VAMP at the same site as TeNT-LC, did not require stimulation. Because TeNT-LC requires the N-terminal coil domain of VAMP for binding but BoNT/B-LC requires the C-terminal coil domain, it seems that, before nerve activity, the N-terminal domain is shielded in a protein complex, but the C-terminal domain is exposed. This N-terminal complex lasts until nerve activity occurs and may serve to cock synaptic vesicles for immediate exocytosis upon Ca2+ entry.
Hua
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Physiology Department, MSB, Rm 3232, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Charlton
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MP
D000818:Animals; D003400:Astacoidea; D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D013744:Tetanus Toxin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D013744:Tetanus Toxin; D033921:Vesicular Transport Proteins; D001905:Botulinum Toxins; D002118:Calcium