The formation of the nervous system involves establishing complex networks of synaptic connections between proper partners. This developmental undertaking requires the rapid expansion of the plasma membrane surface area as neurons grow and polarize, extending axons through the extracellular environment. Critical to the expansion of the plasma membrane and addition of plasma membrane material is exocytic vesicle fusion, a regulated mechanism driven by soluble N-ethylmaleimide-sensitive factor attachment proteins receptors (SNAREs). Since their discovery, SNAREs have been implicated in several critical neuronal functions involving exocytic fusion in addition to synaptic transmission, including neurite initiation and outgrowth, axon specification, axon extension, and synaptogenesis. Decades of research have uncovered a rich variety of SNARE expression and function. The basis of SNARE-mediated fusion, the opening of a fusion pore, remains an enigmatic event, despite an incredible amount of research, as fusion is not only heterogeneous but also spatially small and temporally fast. Multiple modes of exocytosis have been proposed, with full-vesicle fusion (FFV) and kiss-and-run (KNR) being the best described. Whereas most in vitro work has reconstituted fusion using VAMP-2, SNAP-25, and syntaxin-1; there is much to learn regarding the behaviors of distinct SNARE complexes. In the past few years, robust heterogeneity in the kinetics and fate of the fusion pore that varies by cell type have been uncovered, suggesting a paradigm shift in how the modes of exocytosis are viewed is warranted. Here, we explore both classic and recent work uncovering the variety of SNAREs and their importance in the development of neurons, as well as historical and newly proposed modes of exocytosis, their regulation, and proteins involved in the regulation of fusion kinetics.

神经系统的形成涉及在适当的伙伴之间建立复杂的突触连接网络。这项发育任务需要随着神经元的生长和极化而迅速扩大质膜表面积，从而将轴突延伸到细胞外环境。质膜扩张和质膜材料添加的关键是胞吐囊泡融合，这是一种由可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (SNARE) 驱动的调节机制。自发现以来，SNARE 与除了突触传递外还涉及胞吐融合的几种关键神经元功能有关，包括神经突起始和生长、轴突规范、轴突延伸和突触发生。数十年的研究揭示了 SNARE 的丰富表达和功能。尽管进行了大量的研究，但 SNARE 介导的融合的基础，即融合孔的打开，仍然是一个神秘的事件，因为融合不仅是异质的​​，而且空间小、时间快。已经提出了多种胞吐作用模式，其中最好描述的是全囊泡融合（FFV）和接吻运行（KNR）。而大多数体外工作已使用 VAMP-2、SNAP-25 和 syntaxin-1 重建融合；关于不同 SNARE 复合体的行为，还有很多东西需要学习。在过去的几年中，人们发现了融合孔的动力学和命运因细胞类型而异的强烈异质性，这表明如何看待胞吐作用模式的范式转变是有必要的。在这里，我们探讨了经典和最近的工作，揭示了 SNARE 的多样性及其在神经元发育中的重要性，以及历史和新提出的胞吐作用模式、它们的调节以及参与融合动力学调节的蛋白质。