Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion
Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion
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DOI：
10.1038/415646a
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发表时间：
2002-02-07
期刊：
影响因子：
64.8
通讯作者：
Davletov, B
中科院分区：
文献类型：
--
作者：
Hu, K;Carroll, J;Davletov, B
神经递质的释放发生在突触囊泡与质膜融合时。这种神经元胞吐作用由钙触发，需要三种SNARE（可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体）蛋白：突触囊泡上的小突触蛋白（也称为VAMP），以及质膜上的突触融合蛋白和SNAP-25（1-4）。神经元SNARE蛋白形成一个平行的四螺旋束，被认为是驱动相对膜的融合（5，6）。由于这种SNARE复合物在溶液中的形成不需要钙，因此尚不清楚钙在触发SNARE介导的膜融合中具有什么功能。我们现在证明，而syntaxin和SNAP-25在靶膜是自由的陷阱复合物的形成，突触囊泡上的小突触泡蛋白的可用性是非常有限的。微摩尔浓度的钙触发SNARE复合物的形成和突触囊泡与重组靶膜之间的融合。虽然钙确实促进了SNARE蛋白在相对膜之间的相互作用，但它并不通过从突触囊泡限制中释放小突触泡蛋白来起作用。相反，我们的数据表明，钙触发的膜附着机制，使syntaxin和SNAP-25从事小突触蛋白，导致膜融合。
Release of neurotransmitter occurs when synaptic vesicles fuse with the plasma membrane. This neuronal exocytosis is triggered by calcium and requires three SNARE (soluble-N-ethylmaleimide-sensitive factor attachment protein receptors) proteins: synaptobrevin (also known as VAMP) on the synaptic vesicle, and syntaxin and SNAP-25 on the plasma membrane(1-4). Neuronal SNARE proteins form a parallel four-helix bundle that is thought to drive the fusion of opposing membranes(5,6). As formation of this SNARE complex in solution does not require calcium, it is not clear what function calcium has in triggering SNARE-mediated membrane fusion. We now demonstrate that whereas syntaxin and SNAP-25 in target membranes are freely available for SNARE complex formation, availability of synaptobrevin on synaptic vesicles is very limited. Calcium at micromolar concentrations triggers SNARE complex formation and fusion between synaptic vesicles and reconstituted target membranes. Although calcium does promote interaction of SNARE proteins between opposing membranes, it does not act by releasing synaptobrevin from synaptic vesicle restriction. Rather, our data suggest a mechanism in which calcium-triggered membrane apposition enables syntaxin and SNAP-25 to engage synaptobrevin, leading to membrane fusion.