Glutamate synaptic vesicle docking and priming

Docking occurs once the synaptic vesicle has moved from the cytoplasm to a region apposed to the plasma membrane. The vesicle is held in close apposition to the plasma membrane by several proteins that bridge the synaptic vesicle to the plasma membrane. Some of these proteins are in the plasma membrane while others are in the synaptic vesicle. Vesicle fusion is preceded by a priming event where molecular interactions between the docked vesicle and the plasma membrane undergo changes. The molecules in the docking and the priming process are known, however, the exact sequence and the precise molecular changes involved in docking and priming are not well dissected. In this reaction the process of docking and priming has been condensed. It is known that Munc18 along with its interactors is critical for membrane docking and fusion events while Munc 13 along with its interacting proteins is central to priming. Munc 13 could act as a positive regulator for the priming recation. Finally the primed fusion complex is clamped in the pre-fusion form by a Complexin. Complexins are Ca2+ independent cytosolic proteins that bind to partly or fully assembled SNARE complexes. Complexins play both a positive and a negative role in the release process.

神经突触囊泡一旦从细胞质移动至紧邻质膜的区域，便发生对接现象。数种蛋白质通过连接突触囊泡与质膜，将囊泡稳固地维持在质膜附近。其中一些蛋白质位于质膜上，而另一些则存在于突触囊泡内。囊泡融合之前，对接的囊泡与质膜之间的分子相互作用将发生一系列变化，此过程被称为预融合事件。尽管对接和预融合过程中涉及的分子已知，但它们的确切序列和具体分子变化尚未得到充分解析。在本反应中，对接和预融合过程已被简化。已知Munc18及其相互作用蛋白对于膜对接和融合事件至关重要，而Munc 13及其相互作用蛋白在预融合过程中扮演核心角色。Munc 13可能作为预融合反应的正向调节因子。最终，预融合复合物被Complexin固定在预融合状态。Complexin是一种Ca2+非依赖性细胞质蛋白，能够结合部分或完全组装的SNARE复合物。Complexin在释放过程中既发挥正向作用，也发挥负向作用。