Acuna Claudio, Guo Qingchen, Burré Jacqueline, Sharma Manu, Sun Jianyuan, Südhof Thomas C
Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, 265 Campus Drive, Stanford, CA 94305-5453, USA.
Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Neuron. 2014 Jun 4;82(5):1088-100. doi: 10.1016/j.neuron.2014.04.020.
SNARE-complex assembly mediates synaptic vesicle fusion during neurotransmitter release and requires that the target-SNARE protein syntaxin-1 switches from a closed to an open conformation. Although many SNARE proteins are available per vesicle, only one to three SNARE complexes are minimally needed for a fusion reaction. Here, we use high-resolution measurements of synaptic transmission in the calyx-of-Held synapse from mutant mice in which syntaxin-1 is rendered constitutively open and SNARE-complex assembly is enhanced to examine the relation between SNARE-complex assembly and neurotransmitter release. We show that enhancing SNARE-complex assembly dramatically increases the speed of evoked release, potentiates the Ca(2+)-affinity of release, and accelerates fusion-pore expansion during individual vesicle fusion events. Our data indicate that the number of assembled SNARE complexes per vesicle during fusion determines the presynaptic release probability and fusion kinetics and suggest a mechanism whereby proteins (Munc13 or RIM) may control presynaptic plasticity by regulating SNARE-complex assembly.
SNARE复合体组装在神经递质释放过程中介导突触小泡融合，并且需要靶标SNARE蛋白 syntaxin-1从封闭构象转变为开放构象。尽管每个小泡有许多SNARE蛋白，但融合反应最少只需要一到三个SNARE复合体。在这里，我们利用来自突变小鼠的Held壶腹突触中突触传递的高分辨率测量，在这些小鼠中syntaxin-1呈组成型开放且SNARE复合体组装增强，以研究SNARE复合体组装与神经递质释放之间的关系。我们表明，增强SNARE复合体组装会显著提高诱发释放的速度，增强释放的Ca(2+)亲和力，并在单个小泡融合事件中加速融合孔扩张。我们的数据表明，融合过程中每个小泡组装的SNARE复合体数量决定了突触前释放概率和融合动力学，并提出了一种机制，即蛋白质（Munc13或RIM）可能通过调节SNARE复合体组装来控制突触前可塑性。
