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).
Synaptotagmin-3 may play a role in insulin release in
pancreatic β cells, and may also play a role in CXCR4-mediated T-cell migration processes (3).