Munc13和Munc18介导突触小泡启动的分子机制
Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.
作者信息
Lai Ying, Choi Ucheor B, Leitz Jeremy, Rhee Hong Jun, Lee Choongku, Altas Bekir, Zhao Minglei, Pfuetzner Richard A, Wang Austin L, Brose Nils, Rhee JeongSeop, Brunger Axel T
机构信息
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University, Stanford, CA 94305, USA; Department of Photon Science, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
出版信息
Neuron. 2017 Aug 2;95(3):591-607.e10. doi: 10.1016/j.neuron.2017.07.004.
Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca-triggered amplitude and achieves Ca sensitivity at near-physiological concentrations. In Munc13-1/2 double-knockout neurons, expression of a constitutively open mutant of syntaxin could only minimally restore neurotransmitter release relative to Munc13-1 rescue. Together, the physiological functions of Munc13 may be related to regulation of proper SNARE complex assembly.
Munc13催化Syntaxin从与Munc18形成的封闭复合物转变为三元SNARE复合物。在此，我们报道了Munc13的一个独立于Munc18的新功能：在三元SNARE复合物组装过程中，它促进Syntaxin/突触小泡蛋白形成合适的亚结构。与Munc18协同作用时，Munc13还能确保Syntaxin/SNAP-25形成合适的亚结构。在含有SNAREs、结合蛋白和突触结合蛋白的重组融合试验中，同时加入Munc13和Munc18可使钙触发的振幅增加四倍，并在接近生理浓度时实现钙敏感性。在Munc13-1/2双敲除神经元中，Syntaxin组成型开放突变体的表达相对于Munc13-1挽救而言，只能使神经递质释放得到最小程度的恢复。总之，Munc13的生理功能可能与调节合适的SNARE复合物组装有关。
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