Synaptotagmins constitute a family of membrane trafficking proteins that are characterized by an N-terminal transmembrane region (TMR), a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 15 members in the mammalian synaptotagmin family. There are several C2-domain containing protein families that are related to synaptotagmins, including transmembrane (Ferlins, E-Syts, and MCTPs) and soluble (RIMs, Munc13s, synaptotagmin-related proteins and B/K) proteins.
The synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. Calcium binding to synaptotagmin participates in triggering neurotransmitter release at the synapse. The first domain mediates Ca(2+)-dependent phospholipid binding. The second C2 domain mediates interaction with Stonin 2.
Synaptotagmin may have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2 (1, 2).