Major recent advances and previous data have led to a plausible model of how key proteins mediate neurotransmitter release. In this model, the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) proteins syntaxin-1, SNAP-25, and synaptobrevin form tight complexes that bring the membranes together and are crucial for membrane fusion. NSF and SNAPs disassemble SNARE complexes and ensure that fusion occurs through an exquisitely regulated pathway that starts with Munc18-1 bound to a closed conformation of syntaxin-1. Munc18-1 also binds to synaptobrevin, forming a template to assemble the SNARE complex when Munc13-1 opens syntaxin-1 while bridging the vesicle and plasma membranes. Synaptotagmin-1 and complexin bind to partially assembled SNARE complexes, likely stabilizing them and preventing fusion until Ca2+ binding to synaptotagmin-1 causes dissociation from the SNARE complex and induces interactions with phospholipids that help trigger release. Although fundamental questions remain about the mechanism of membrane fusion, these advances provide a framework to investigate the mechanisms underlying presynaptic plasticity.

中文翻译：

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神经递质释放的分子机制

最近的重大进展和之前的数据已经建立了一个关于关键蛋白质如何介导神经递质释放的合理模型。在此模型中，可溶性 N-乙基马来酰亚胺敏感因子 (NSF) 附着蛋白 (SNAP) 受体 (SNARE) 蛋白 Syntaxin-1、SNAP-25 和 synaptobrevin 形成紧密的复合物，将膜结合在一起，对于膜融合至关重要。 NSF 和 SNAP 分解 SNARE 复合物，并确保融合通过一条精心调控的途径发生，该途径从与 Syntaxin-1 闭合构象结合的 Munc18-1 开始。 Munc18-1 还与突触短蛋白结合，当 Munc13-1 打开 Syntaxin-1 同时桥接囊泡和质膜时，形成模板来组装 SNARE 复合物。 Synaptotagmin-1 和复合蛋白与部分组装的 SNARE 复合物结合，可能稳定它们并防止融合，直到 Ca2+与 synaptotagmin-1 结合会导致 SNARE 复合物解离，并诱导与磷脂相互作用，从而帮助触发释放。尽管关于膜融合机制的基本问题仍然存在，但这些进展为研究突触前可塑性的机制提供了一个框架。