Synaptotagmin regulation of coated pit assembly

Synaptotagmins bind clathrin AP-2 with high affinity via their second C-2 d omain, which indicates they are involved in coated pit function. We now rep ort that expression of synaptotagmins lacking either the second C-2 domain or the entire cytoplasmic region potently inhibit endocytosis. Inhibition w as dependent on two intramembrane cysteine residues that were found to be e ssential for synaptotagmin oligomerization. Cells expressing the wild-type, but not the mutant, truncated synaptotagmin fragment had a reduced number of clathrin-coated pits. These results suggest that the formation of synapt otagmin multimers is an important step in the regulation of coated pit asse mbly.