Activity-dependent changes in partial VAMP complexes during neurotransmitter release

Abstract

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 occurrs and may serve to cock synaptic vesicles for immediate exocytosis upon Ca²⁺ entry.