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首页> 外文期刊>Neuron >Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18
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Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18

机译:Munc13和Munc18的突触囊泡引发的分子机制

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摘要

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 Ca2+-triggered amplitude and achieves Ca2+ 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.
机译:Munc13催化与闭合络合物的粘合素的运输与Munc18中的闭合复合物进入三元蛇形复合物。 在这里,我们报告了Munc13的新功能,独立于Munc18:它促进了三元链条复合体的组装期间促进了适当的Syntaxin / Synaptobrevin子配置。 与Munc18合作,MunC13还可确保适当的Syntaxin / Snap-25子配置。 在具有捕获,复合素和Sysaptotagmin的重构融合测定中,包含Munc13和Munc18四重组Ca2 + - 触发幅度,并在接近生理浓度下实现Ca2 +敏感性。 在Munc13-1 / 2双敲除神经元中,棘突蛋白的组成型突变体的表达只能相对于Munc13-1救援最低恢复神经递质释放。 在一起,Munc13的生理功能可能与适当的圈套复杂组件的调节有关。

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  • 来源
    《Neuron》 |2017年第3期|共27页
  • 作者单位

    Stanford Univ Dept Mol &

    Cellular Physiol Stanford CA 94305 USA;

    Stanford Univ Dept Mol &

    Cellular Physiol Stanford CA 94305 USA;

    Stanford Univ Dept Mol &

    Cellular Physiol Stanford CA 94305 USA;

    Max Planck Inst Expt Med Dept Mol Neurobiol D-37075 Gottingen Germany;

    Max Planck Inst Expt Med Dept Mol Neurobiol D-37075 Gottingen Germany;

    Max Planck Inst Expt Med Dept Mol Neurobiol D-37075 Gottingen Germany;

    Stanford Univ Dept Mol &

    Cellular Physiol Stanford CA 94305 USA;

    Stanford Univ Dept Mol &

    Cellular Physiol Stanford CA 94305 USA;

    Stanford Univ Dept Mol &

    Cellular Physiol Stanford CA 94305 USA;

    Max Planck Inst Expt Med Dept Mol Neurobiol D-37075 Gottingen Germany;

    Max Planck Inst Expt Med Dept Mol Neurobiol D-37075 Gottingen Germany;

    Stanford Univ Dept Mol &

    Cellular Physiol Stanford CA 94305 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

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