Neurotransmitter release, hormone secretion and a variety of other secretor
y process are tightly regulated with exocytotic fusion of secretory vesicle
s being triggered by a rise in cytosolic Ca2+ concentration. A series of pr
oteins that act as part of a conserved core machinery for vesicle docking a
nd fusion throughout the cell have been identified. In regulated exocytosis
this core machinery must be controlled by Ca2+-sensor proteins that allow
rapid activation of the fusion process following elevation of cytosolic Ca2
+ concentration. The properties of such Ca2+ sensors are known from physiol
ogical studies but their molecular identity remains to be unequivocally est
ablished. The multiple Ca2+-dependent steps in the exocytotic pathway sugge
st the likely involvement of several Ca2+-binding proteins with distinct pr
operties. Functional evidence for the role of various Ca2+-binding proteins
and their possible sites of action is accumulating but a definitive identi
fication of the major Ca2+-sensor in the final step of Ca2+-triggered membr
ane fusion in different cell types awaits further analysis.