《Cell》：唐炅发表最新神经学研究成果

生物谷

        突触结合蛋白(synaptotagmin)Ⅰ是神经细胞突触囊泡上的一个膜整合蛋白。近年来的研究表明，突触结合蛋白Ⅰ在Ca2+引发的神经递质快速释放过程中起到Ca2+感受器的作用。Ca2+与突触结合蛋白1（synaptotagmin1）结合能够触发快速的突触囊泡的外分泌过程。

        除了突触结合蛋白I外，由Ca2+触发的快速胞外分泌还需要complexins。突触结合蛋白I和complexin都能与装配好的SNARE复合体结合。SNARE(Soluble  N-ethyl-maleimide  sensitive  fusion  protein  attachment  protein  receptor)复合体是在突触囊泡和突触前膜融合过程中的基本元件。但是，目前还不清楚它们的功能如何偶联在一起。

        在最新一期的Cell杂志上，来自美国得克萨斯州大学西南医学中心的华人研究人员唐炅（Jiong  Tang，文章的第一作者）和他的同事推测，complexin的结合能活化SNARE复合体，将其变成一种可转移状态，并且钙离子与突触结合蛋白的结合通过从可转移SNARE复合体置换complexin来引发快速的胞外分泌。

        值得一提的是，研究人员证实，在生化水平上，突触结合蛋白I能够与complexin竞争SNARE复合体结合位点，因此能以一种依赖钙离子的方式将complexin从SNARE复合体上移走。

        有选择性地增加局部区域的complexin浓度能够削弱钙离子引发的快速胞外分泌，但能保持其他形式的SNARE依赖性融合。

        研究人员提出的这种钙离子诱导的将complexin从SNARE复合体上置换下来从而引发快速的胞外分泌的理论能够解释complexin的功能丧失和获得的变化，并且为高速的、同步的钙离子触发的快速神经递质释放过程给出了一种分子水平的解释。

部分英文原文：

A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis

Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca(2+)-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca(2+)-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca(2+)-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca(2+)-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca(2+)-triggered neurotransmitter release.