Department of Pharmacology, University of Michigan, Ann Arbor, MI.
Department of Chemistry, University of Colorado, Denver, CO.
J Gen Physiol. 2018 Jun 4;150(6):783-807. doi: 10.1085/jgp.201711944. Epub 2018 May 24.
Synaptotagmin (Syt) proteins comprise a 17-member family, many of which trigger exocytosis in response to calcium. Historically, most studies have focused on the isoform Syt-1, which serves as the primary calcium sensor in synchronous neurotransmitter release. Recently, Syt-7 has become a topic of broad interest because of its extreme calcium sensitivity and diversity of roles in a wide range of cell types. Here, we review the known and emerging roles of Syt-7 in various contexts and stress the importance of its actions. Unique functions of Syt-7 are discussed in light of recent imaging, electrophysiological, and computational studies. Particular emphasis is placed on Syt-7-dependent regulation of synaptic transmission and neuroendocrine cell secretion. Finally, based on biochemical and structural data, we propose a mechanism to link Syt-7's role in membrane fusion with its role in subsequent fusion pore expansion via strong calcium-dependent phospholipid binding.
突触结合蛋白（Syt）蛋白家族由 17 个成员组成，其中许多成员在钙响应时触发胞吐作用。历史上，大多数研究都集中在 Syt-1 同工型上，它是同步神经递质释放的主要钙传感器。最近，由于 Syt-7 具有极高的钙敏感性和在多种细胞类型中的多种作用，它已成为广泛关注的话题。在这里，我们综述了 Syt-7 在各种情况下的已知和新兴作用，并强调了其作用的重要性。根据最近的成像、电生理学和计算研究，讨论了 Syt-7 的独特功能。特别强调了 Syt-7 对突触传递和神经内分泌细胞分泌的依赖调节。最后，根据生化和结构数据，我们提出了一种机制，将 Syt-7 在膜融合中的作用与其通过强钙依赖性磷脂结合在随后的融合孔扩张中的作用联系起来。
