Calcium Control of Neurotransmitter Release
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Open Access
- 8 November 2011
- journal article
- review article
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Perspectives in Biology
- Vol. 4 (1), a011353
- https://doi.org/10.1101/cshperspect.a011353
Abstract
Upon entering a presynaptic terminal, an action potential opens Ca2+ channels, and transiently increases the local Ca2+ concentration at the presynaptic active zone. Ca2+ then triggers neurotransmitter release within a few hundred microseconds by activating synaptotagmins Ca2+. Synaptotagmins bind Ca2+ via two C2-domains, and transduce the Ca2+ signal into a nanomechanical activation of the membrane fusion machinery; this activation is mediated by the Ca2+-dependent interaction of the synaptotagmin C2-domains with phospholipids and SNARE proteins. In triggering exocytosis, synaptotagmins do not act alone, but require an obligatory cofactor called complexin, a small protein that binds to SNARE complexes and simultaneously activates and clamps the SNARE complexes, thereby positioning the SNARE complexes for subsequent synaptotagmin action. The conserved function of synaptotagmins and complexins operates generally in most, if not all, Ca2+-regulated forms of exocytosis throughout the body in addition to synaptic vesicle exocytosis, including in the degranulation of mast cells, acrosome exocytosis in sperm cells, hormone secretion from endocrine cells, and neuropeptide release.Keywords
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