Activity-dependent changes in partial VAMP complexes during neurotransmitter release

The temporal sequence of SNARE protein interactions that cause exocytosis i s unknown. Blockade of synaptic neurotransmitter release through cleavage o f VAMP/synaptobrevin by tetanus toxin light chain (TeNT-LC) was accelerated by nerve stimulation. Botulinum/B neurotoxin light chain (BoNT/B-LC), whic h cleaves VAMP at the same site as TeNT-LC, did not require stimulation. Be cause TeNT-LC requires the N-terminal coil domain of VAMP for binding but B oNT/B-LC requires the C-terminal coil domain, it seems that, before nerve a ctivity, the N-terminal domain is shielded in a protein complex, but the C- terminal domain is exposed. This N-terminal complex lasts until nerve activ ity occurrs and may serve to cock synaptic vesicles for immediate exocytosi s upon Ca2+ entry.