Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, FL 33136, U.S.A.
Biochem Soc Trans. 2024 Aug 28;52(4):1715-1725. doi: 10.1042/BST20231333.
Various cell types release neurotransmitters, hormones and many other compounds that are stored in secretory vesicles by exocytosis via the formation of a fusion pore traversing the vesicular membrane and the plasma membrane. This process of membrane fusion is mediated by the Soluble N-ethylmaleimide-Sensitive Factor Attachment Proteins REceptor (SNARE) protein complex, which in neurons and neuroendocrine cells is composed of the vesicular SNARE protein Synaptobrevin and the plasma membrane proteins Syntaxin and SNAP25 (Synaptosomal-Associated Protein of 25 kDa). Before a vesicle can undergo fusion and release of its contents, it must dock at the plasma membrane and undergo a process named 'priming', which makes it ready for release. The primed vesicles form the readily releasable pool, from which they can be rapidly released in response to stimulation. The stimulus is an increase in Ca2+ concentration near the fusion site, which is sensed primarily by the vesicular Ca2+ sensor Synaptotagmin. Vesicle priming involves at least the SNARE proteins as well as Synaptotagmin and the accessory proteins Munc18, Munc13, and Complexin but additional proteins may also participate in this process. This review discusses the current views of the interactions and the structural changes that occur among the proteins of the vesicle priming machinery.
各种细胞类型通过胞吐作用释放神经递质、激素和许多其他储存在分泌小泡中的化合物，通过形成穿过小泡膜和质膜的融合孔来实现。这种膜融合过程由可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白复合物介导，在神经元和神经内分泌细胞中，该复合物由囊泡 SNARE 蛋白突触融合蛋白和质膜蛋白Syntaxin 和 SNAP25（突触相关蛋白 25 kDa）组成。在囊泡能够融合并释放其内容物之前，它必须停靠在质膜上并经历一个名为“引发”的过程，该过程使其为释放做好准备。引发的囊泡形成易于释放的池，从中可以迅速释放以响应刺激。刺激是融合部位附近 Ca2+浓度的增加，这主要由囊泡 Ca2+传感器突触融合蛋白感知。囊泡引发至少涉及 SNARE 蛋白以及突触融合蛋白和辅助蛋白 Munc18、Munc13 和 Complexin，但其他蛋白也可能参与该过程。这篇综述讨论了囊泡引发机制中蛋白相互作用和结构变化的当前观点。
