How Synaptotagmin Promotes Membrane Fusion

作者：Sascha Martens, Michael M. Kozlov, Harvey T. McMahon · 发表于：Science · 年份：2007 · DOI：10.1126/science.1142614 · 被引用次数：550 · 研究领域：Cellular transport and secretion、Lipid Membrane Structure and Behavior、Calcium signaling and nucleotide metabolism

Synaptic vesicles loaded with neurotransmitters are exocytosed in a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent manner after presynaptic depolarization induces calcium ion (Ca2+) influx. The Ca2+ sensor required for fast fusion is synaptotagmin-1. The activation energy of bilayer-bilayer fusion is very high (approximately 40 k(B)T). We found that, in response to Ca2+ binding, synaptotagmin-1 could promote SNARE-mediated fusion by lowering this activation barrier by inducing high positive curvature in target membranes on C2-domain membrane insertion. Thus, synaptotagmin-1 triggers the fusion of docked vesicles by local Ca2+-dependent buckling of the plasma membrane together with the zippering of SNAREs. This mechanism may be widely used in membrane fusion.