Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.
Cold Spring Harb Perspect Biol. 2012 Jan 1;4(1):a011353. doi: 10.1101/cshperspect.a011353.
Upon entering a presynaptic terminal, an action potential opens Ca(2+) channels, and transiently increases the local Ca(2+) concentration at the presynaptic active zone. Ca(2+) then triggers neurotransmitter release within a few hundred microseconds by activating synaptotagmins Ca(2+). Synaptotagmins bind Ca(2+) via two C2-domains, and transduce the Ca(2+) signal into a nanomechanical activation of the membrane fusion machinery; this activation is mediated by the Ca(2+)-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, Ca(2+)-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.
当动作电位进入突触前末梢时，会打开钙离子通道，使突触前活跃区的局部钙离子浓度短暂升高。钙离子通过激活突触融合蛋白相关蛋白 Ca2+（synaptotagmins Ca2+），在几百微秒内触发神经递质释放。突触融合蛋白通过两个 C2 结构域与钙离子结合，并将钙离子信号转导为膜融合机制的纳米机械激活；这种激活是通过突触融合蛋白 C2 结构域与磷脂和 SNARE 蛋白的 Ca2+依赖性相互作用介导的。在触发胞吐作用时，突触融合蛋白并非单独作用，而是需要一种必需的辅助因子称为复合蛋白，它是一种与 SNARE 复合物结合并同时激活和固定 SNARE 复合物的小蛋白，从而使 SNARE 复合物为随后的突触融合蛋白作用做好准备。除了突触囊泡胞吐作用外，突触融合蛋白和复合蛋白的保守功能通常在体内大多数（如果不是全部）钙离子调节的胞吐作用中发挥作用，包括肥大细胞脱颗粒、精子细胞顶体胞吐作用、内分泌细胞激素分泌和神经肽释放。
