Synaptobrevin-2 (Syb2) is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) that is essential for neurotransmitter release. It is the most numerous protein on a synaptic vesicle (SV) and drives SV fusion via interactions with its cognate SNARE partners on the presynaptic plasma membrane. Synaptophysin (Syp) is the second most abundant protein on SVs; however, in contrast to Syb2, it has no obligatory role in neurotransmission. Syp interacts with Syb2 on SVs, and the molecular nature of its interaction with Syb2 and its physiological role has been debated for decades. However, recent studies have revealed that the sole physiological role of Syp at the presynapse is to ensure the efficient retrieval of Syb2 during SV endocytosis. In this review, current theories surrounding the role of Syp in Syb2 trafficking will be discussed, in addition to the debate regarding the molecular nature of their interaction. A unifying model is presented that describes how Syp controls Syb2 function as part of an integrated mechanism involving key molecular players such as intersectin-1 and AP180/CALM. Finally, key future questions surrounding the role of Syp-dependent Syb2 trafficking will be posed, with respect to brain function in health and disease.

中文翻译：

---

突触素依赖性 synaptobrevin-2 在突触前机制和功能中的转运

Synaptobrevin-2 (Syb2) 是一种可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体 (SNARE)，对神经递质释放至关重要。它是突触小泡 (SV) 上数量最多的蛋白质，并通过与其在突触前质膜上的同源 SNARE 伙伴的相互作用来驱动 SV 融合。突触素 (Syp) 是 SV 上第二丰富的蛋白质；然而，与 Syb2 相比，它在神经传递中没有强制性作用。Syp 在 SV 上与 Syb2 相互作用，其与 Syb2 相互作用的分子性质及其生理作用已争论了几十年。然而，最近的研究表明，Syp 在突触前的唯一生理作用是确保在 SV 内吞过程中有效检索 Syb2。在这篇评论中，除了关于它们相互作用的分子性质的争论外，还将讨论围绕 Syp 在 Syb2 贩运中的作用的当前理论。提出了一个统一模型，该模型描述了 Syp 如何控制 Syb2 作为涉及关键分子参与者（如 intersectin-1 和 AP180/CALM）的综合机制的一部分。最后，将提出围绕 Syp 依赖性 Syb2 贩运的作用的未来关键问题，以及大脑在健康和疾病中的功能。