Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Trends Cell Biol. 2018 Aug;28(8):631-645. doi: 10.1016/j.tcb.2018.03.004. Epub 2018 Apr 26.
Recent structural and functional studies of the synaptic vesicle fusion machinery suggest an inhibited tripartite complex consisting of neuronal soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs), synaptotagmin, and complexin prior to Ca-triggered synaptic vesicle fusion. We speculate that Ca-triggered fusion commences with the release of inhibition by Ca binding to synaptotagmin C2 domains. Subsequently, fusion is assisted by SNARE complex zippering and by active membrane remodeling properties of synaptotagmin. This additional, inhibitory role of synaptotagmin may be a general principle since other recent studies suggest that Ca binding to extended synaptotagmin C2 domains enables lipid transport by releasing an inhibited state of the system, and that Munc13 may nominally be in an inhibited state, which is released upon Ca binding to one of its C2 domains.
近期关于突触囊泡融合机制的结构和功能研究表明，在钙离子触发的突触囊泡融合之前，存在一个受抑制的三联体复合物，由神经元可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体（SNAREs）、突触融合蛋白和伴肌动蛋白组成。我们推测，钙离子触发的融合始于钙离子结合突触融合蛋白 C2 结构域释放抑制作用。随后，SNARE 复合物的拉链作用和突触融合蛋白的主动膜重塑特性辅助融合的发生。突触融合蛋白的这种额外的抑制作用可能是一个普遍的原则，因为最近的其他研究表明，钙离子结合扩展的突触融合蛋白 C2 结构域可以通过释放系统的抑制状态来促进脂质运输，而且 Munc13 可能名义上处于抑制状态，当它的一个 C2 结构域结合钙离子时，这种抑制状态会被释放。
