Complexins regulate a late step in Ca2+-dependent neurotransmitter release

Synaptic vesicle fusion at synapses is triggered by increases in cytosolic Ca2+ levels. However, the identity of the Ca2+ sensor and the transduction mechanism of the Ca2+ trigger are unknown. We show that Complexins, stoichi ometric components of the exocytotic core complex, are important regulators of transmitter release at a step immediately preceding vesicle fusion. Neu rons lacking Complexins show a dramatically reduced transmitter release eff iciency due to decreased Ca2+ sensitivity of the synaptic secretion process . Analyses of mutant neurons demonstrate that Complexins are acting at or f ollowing the Ca2+-triggering step of fast synchronous transmitter release b y regulating the exocytotic Ca2+ sensor, its interaction with the core comp lex fusion machinery, or the efficiency of the fusion apparatus itself.