Regulation of transmitter release by Unc-13 and its homologues

Neurotransmitters are released by Ca(2+)-triggered exocytotic fusion of synaptic vesicles. Before fusion, vesicles dock at a specialised presynaptic plasma membrane region, the active zone, where they are primed to a fusion competent state. The nature of this priming reaction has long been enigmatic. Recent evidence demonstrates that priming is an essential and rate-limiting step in secretion from neurons and neuroendocrine cells. Members of the Unc-13 protein family, which are highly conserved during evolution and act as novel targets of the diacylglycerol second-messenger pathway, have been identified to play an essential role in this process.