Calcium sensors in regulated exocytosis

Neurotransmitter release, hormone secretion and a variety of other secretory process are tightly regulated with exocytotic fusion of secretory vesicles being triggered by a rise in cytosolic Ca2+ concentration. A series of proteins that act as part of a conserved core machinery for vesicle docking and 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 physiological studies but their molecular identity remains to be unequivocally established. The multiple Ca2+-dependent steps in the exocytotic pathway suggest the likely involvement of several Ca2+-binding proteins with distinct properties. Functional evidence for the role of various Ca2+-binding proteins and their possible sites of action is accumulating but a definitive identification of the major Ca2+-sensor in the final step of Ca2+-triggered membrane fusion in different cell types awaits further analysis.