Abstract：
Calcium (Ca2+) plays a critical role in triggering all three primary modes of neurotransmitter release (synchronous, asynchronous, and spontaneous). Synaptotagmin1, a protein with two C2 domains, is the first isoform of the synaptotagmin family that was identified and demonstrated as the primary Ca2+ sensor for synchronous neurotransmitter release. Other isoforms of the synaptotagmin family as well as other C2 proteins such as the double C2 domain protein family were found to act as Ca2+ sensors for different modes of neurotransmitter release. Major recent advances and previous data suggest a new model, release-of-inhibition, for the initiation of Ca2+-triggered synchronous neurotransmitter release. Synaptotagmin1 binds Ca2+ via its two C2 domains and relieves a primed pre-fusion machinery. Before Ca2+ triggering, synaptotagmin1 interacts Ca2+ independently with partially zippered SNARE complexes, the plasma membrane, phospholipids, and other components to form a primed pre-fusion state that is ready for fast release. However, membrane fusion is inhibited until the arrival of Ca2+ reorients the Ca2+-binding loops of the C2 domain to perturb the lipid bilayers, help bridge the membranes, and/or induce membrane curvatures, which serves as a power stroke to activate fusion. This chapter reviews the evidence supporting these models and discusses the molecular interactions that may underlie these abilities.
摘要：
钙（Ca2+）在触发所有三种主要神经递质释放模式（同步，异步，和自发)。Synaptotagmin1，具有两个C2结构域的蛋白质，是突触结合蛋白家族的第一个同工型，已被鉴定并证明是用于同步神经递质释放的主要Ca2传感器。发现突触蛋白家族的其他同工型以及其他C2蛋白，例如双C2结构域蛋白家族，可充当不同神经递质释放模式的Ca2传感器。最近的重大进展和以前的数据表明了一种新的模式，释放抑制，用于启动Ca2+触发的同步神经递质释放。Synaptotagmin1通过其两个C2结构域结合Ca2并缓解引发的融合前机制。在Ca2+触发之前，synaptotagmin1与部分拉链SNARE复合物独立地相互作用Ca2+，质膜，磷脂，和其他组件，以形成准备快速释放的预融合状态。然而,膜融合被抑制，直到Ca2+的到达重新定向C2域的Ca2+结合环扰乱脂质双层，帮助桥接膜，和/或诱导膜弯曲，作为动力冲程来激活融合。本章回顾了支持这些模型的证据，并讨论了可能构成这些能力的分子相互作用。
