Synaptotagmin is a synaptic vesicle membrane protein that is postulated to function as a calcium (Ca2+) sensor for neurotransmitter release. This protein contains two Ca2+-binding domains (C2A, C2B) in its cytoplasmic region. Genetic studies provide strong evidence supporting the idea that synaptotagmin is the Ca2+ sensor for the fast synchronous component of evoked transmitter release. In addition, synaptotagmin appears to be involved in docking and priming (by clamping spontaneous fusion) of synaptic vesicles and regulating fusion pores as well as vesicle endocytosis. In vitro studies demonstrate that synaptotagmin binds to phospholipid membranes in the presence and absence of Ca2+. Furthermore, in response to Ca2+, the tips of synaptotagmin C2 domains penetrate lipid bilayers, altering the membrane curvature. Synaptotagmin also binds to the soluble Nethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that is believed to be the core fusion machinery, although the findings on the Ca2+ dependency of binding of synaptotagmin to SNARE have been inconsistent and controversial. Taken together, synaptotagmin appears to trigger a fast synchronous component of transmitter release by binding to Ca2+, probably through the interactions with both membranes and SNAREs.
- Synaptic vesicle
- Synchronous release
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)