Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
Annu Rev Cell Dev Biol. 2009;25:513-37. doi: 10.1146/annurev.cellbio.24.110707.175239.
Fast exocytosis of synaptic vesicles differs from other membrane fusion reactions by being under tight temporal control by the intracellular calcium concentration. This is achieved by subjecting the SNARE-dependent fusion pathway to additional layers of control, both upstream and downstream of the assembly of the fusogenic SNARE-complex. Here, I review conflicting views on the function of the core fusion machinery consisting of the SNAREs, Munc18, complexin, and synaptotagmin. Munc18 controls docking of vesicles to the plasma membrane and initial SNARE-complex assembly, whereas complexin and synaptotagmin cooperate in holding the SNARE complex in an intermediate release-ready or cocked state. Different effects of complexin and synaptotagmin shape the energy landscape for fusion and make final fusion calcium triggered. The final steps are fusion pore formation and expansion, which allow release of the water-soluble vesicle content. The fusion pore remains the most elusive part of the exocytosis pathway, owing to its short lifetime.
快速的突触小泡胞吐作用通过受细胞内钙离子浓度的严格时间控制而有别于其他膜融合反应。这是通过在融合所需 SNARE 复合物组装的上下游对 SNARE 依赖性融合途径进行额外的控制来实现的。在这里，我回顾了关于由 SNARE、Munc18、complexin 和 synaptotagmin 组成的核心融合机制的功能的相互矛盾的观点。Munc18 控制囊泡与质膜的对接和初始 SNARE 复合物的组装，而 complexin 和 synaptotagmin 共同作用将 SNARE 复合物保持在中间释放准备或上膛状态。complexin 和 synaptotagmin 的不同作用塑造了融合的能量景观，并使最终融合钙离子触发。最后步骤是融合孔的形成和扩展，这允许水溶性囊泡内容物的释放。由于融合孔的寿命很短，因此它仍然是胞吐途径中最难以捉摸的部分。
