Double C2 protein. A review

Concerted effort has led to the identification of dozens of synaptic proteins and has thereby opened the door for the characterisation of the molecular mechanisms underlying regulated exocytosis. Calcium is known to play a number of roles in regulated exocytosis, acting as the trigger for fast synaptic transmission and also acting at some of the steps preceding vesicle fusion. Investigators have therefore focussed considerable attention on possible calcium sensors. What many of the candidate proteins have in common is a C2 domain, one of the four conserved domains originally described in protein kinase C. Such domains have been shown to bind calcium and phospholipid in a large number of intracellular proteins. Synaptotagmin, a C2-domain protein, is a very strong candidate for the protein involved in triggering fast calcium-dependent vesicle fusion. Recent attention has also concerned the other calcium sensors, which may play roles in the 'priming' or transport of vesicles. This review concerns one of these tentative calcium-binding proteins, double C2 or DOC2. DOC2 was originally isolated from nervous tissue but subsequently has been found to be more widely expressed. DOC2 is a vesicular protein that may be involved in the early stages of preparing vesicles for exocytosis.