启动的SNARE-复合素-synaptotagmin复合体用于神经元外细胞形成
Qiangjun Zhou1,2, Peng Zhou1, Austin L Wang1,2
1Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Nature
|August 17, 2017
概括
这项研究揭示了synaptotagmin-1,complexin和SNARE蛋白质如何合作控制神经递质释放. 在Synaptotagmin-1上的两个关键接口对于解锁聚变机制至关重要.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 引起的同步神经递质释放依赖于synaptotagmin,复合素和SNARE蛋白质.
- 它们合作的精确分子机制在很大程度上是未知的.
研究的目的:
- 阐明Synaptotagmin-1,复合素和SNARE蛋白在融合前状态之间的相互作用的结构基础.
- 了解这些相互作用如何调节同步神经递质释放.
主要方法:
- 预先融合的SNARE-complexin-synaptotagmin-1复合物的晶体结构的确定.
- 生物化学测定和突变发生,以评估已识别的接口的功能重要性.
主要成果:
- 除了主要接口外,还揭示了synaptotagmin-1和SNARE复合素捆绑之间的新型三方接口.
- 证明破坏任何接口都会显著损害神经元中引起的同步释放.
- 表明Ca2+与synaptotagmin-1的结合解锁了该复合体,使SNARE拉链和膜融合成为可能.
结论:
- 两种已识别的synaptotagmin-1接口都对原始化前融合状态和同步的神经递质释放至关重要.
- 三方复合物必须由Ca2+解锁才能启动膜融合,这解释了复合素和synaptotagmin-1在定时释放中的作用.
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