Synaptotagmins constitute a family of membrane trafficking
proteins that are characterized by an Nterminal
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-6 is localized to the endoplasmic
reticulum and/or Golgi-like perinuclear compartment. It
may be important for trafficking and calcium signaling as
it is specially expressed in non-neuronal tissues. Also
SytVI is present in the acrosomal region of mammalian
spermatozoa. The cytosolic domain of SytVI can abrogate
exocytosis by competing with the endogenous protein for
essential interactions with the fusion machinery involved
in a acrosomal exocytosis (3-5).