Neurotransmitters are released by Ca2+-triggered exocytotic fusion of synap
tic vesicles. Before fusion, vesicles dock at a specialised presynaptic pla
sma membrane region, the active zone, where they are primed to a fusion com
petent 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 Un
c-13 protein family, which are highly conserved during evolution and act as
novel targets of the diacylglycerol second-messenger pathway, have been id
entified to play an essential role in this process.