Synaptotagmin-7
Domain
The C2 domains bind Ca(2+) and membranes. Binding to membranes involves Ca(2+)-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins. The two C2 domains bind independently to planar membranes, without interdomain cooperativity. Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins.
Function
Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain. Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis. SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins (PubMed:26738595). Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair (By similarity). Ca(2+)-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (PubMed:16982801, PubMed:21041449). Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (PubMed:18539119). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on peroxisomal membranes (PubMed:25860611). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters (PubMed:24569478, PubMed:26738595). Probably mediates synaptic facilitation by directly increasing the probability of release (PubMed:26738595). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin (PubMed:24569478). Also acts as a regulator of Ca(2+)-dependent insulin and glucagon secretion in beta-cells (PubMed:18308938, PubMed:19171650). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (PubMed:20956309). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity).
Post-translational modifications
Palmitoylated at its vesicular N-terminus; palmitoylation is required for localization to lysosome and phagocytosis in macrophages.
Sequence Similarities
Belongs to the synaptotagmin family.
Tissue Specificity
Widely expressed. Expressed in insulin-secreting cells (PubMed:18308938). Present in glucagon-secreting cells (at protein level) (PubMed:19171650).
Cellular localization
- Cell membrane
- Single-pass membrane protein
- Presynaptic cell membrane
- Single-pass membrane protein
- Cytoplasmic vesicle
- Secretory vesicle
- Synaptic vesicle membrane
- Single-pass membrane protein
- Lysosome membrane
- Single-pass membrane protein
- Cytoplasmic vesicle
- Phagosome membrane
- Single-pass membrane protein
- Peroxisome membrane
- Single-pass membrane protein
- Cytoplasmic vesicle
- Secretory vesicle membrane
- Single-pass membrane protein
- Localization to lysosomes is dependent on N-terminal palmitoylation and interaction with CD63.
Alternative names
Synaptotagmin-7, Synaptotagmin VII, SytVII, Syt7