Proteins involved in synaptic vesicle docking and fusion.
Proteins involved in synaptic vesicle docking and fusion.
复制标题
参与突触小泡对接和融合的蛋白质。
DOI：
10.1101/sqb.1995.060.01.038
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Whiteheart,SW
中科院分区：
文献类型：
--
作者：
Burns,ME;Beushausen,SA;Chin,GJ;Tang,D;DeBello,WM;Dresbach,T;O'Connor,V;Schweizer,FE;Wang,SS;Whiteheart,SW
最高级别的膜运输形式之一发生在神经元的突触前末端。在这些结构中，突触囊泡与突触前质膜的融合导致神经递质的胞外释放。这种形式的胞吐的一个显著特点是其严格的调控。电信号（动作电位）到达突触前末端，使胞吐速率加快10万倍以上（Katz 1969）。这种调节是由钙离子的电压依赖性进入和随后的细胞内积聚所赋予的（Augustine et al. 1987）。神经递质胞外分泌的另一个显著特征是其速度。在钙离子进入突触前末端后不到一毫秒的时间内，递质从末端释放并扩散到突触间隙（Llin~ is et al. 1981; Augustine et al. 1985）。神经递质的胞外分泌只是突触囊泡参与的一系列反应中的一个（图1）。充满神经递质的突触囊泡聚集在突触前神经末梢，并停靠在细胞顶的质膜上。这些停靠的囊泡与质膜的紧密接触在形态学上是可区分的，在它们能够融合之前可能经历了几次启动反应（回顾，见Augustine et al. 1996）。当动作电位侵入突触前末端时，钙内流导致这些突触囊泡与质膜融合，将神经递质释放到突触间隙中。融合后，囊泡及其蛋白质成分的内吞作用导致包被囊泡的形成。据信，这些囊泡失去了它们的外壳，并与早期的内体中间体结合。新的突触囊泡从这些中间体中分离出来，充满递质，并重新进入可用于神经递质释放的突触囊泡池（Heuser和Reese 1973）。因此，对神经递质释放的全面理解不仅需要解释囊泡如何融合，还需要解释它们如何能够有效地通过整个胞吐/内吞循环。
One of the most highly evolved forms of membrane trafficking takes place in the presynaptic terminals of neurons. Within these structures, the fusion of synaptic vesicles with the presynaptic plasma membrane leads to the exocytotic release of neurotransmitters. A striking feature of this form of exocytosis is its tight regulation. The arrival of an electrical signal, the action potential, in the presynaptic terminal accelerates the rate of exocytosis more than 100,000-fold (Katz 1969). This regulation is conferred by the voltage-dependent entry, and subsequent intracellular accumulation, of calcium ions (Augustine et al. 1987). Another remarkable feature of the exocytotic secretion of neurotransmitters is its speed. Within a fraction of a millisecond after calcium has entered the presynaptic terminal, transmitter is released from the terminal and diffuses across the synaptic cleft (Llin~ is et al. 1981; Augustine et al. 1985).The exocytotic secretion of neurotransmitters is just one of a cycle of reactions in which synaptic vesicles participate (Fig. 1). Synaptic vesicles filled with neurotransmitter accumulate in presynaptic nerve terminals and become docked at the plasma membrane of the ceil. These docked vesicles, morphologically distinguishable by their close contact with the plasma membrane, probably undergo several priming reactions before they become competent for fusion (for review, see Augustine et al. 1996). When an action potential invades the presynaptic terminal, calcium influx causes fusion of these primed synaptic vesicles with the plasma membrane, releasing neurotransmitter into the synaptic cleft. Following fusion, endocytosis of the vesicle and its protein components results in the formation of coated vesicles. It is believed that these vesicles lose their coats and coalesce with early endosomai intermediates. New synaptic vesicles pinch off from these intermediates, refill with transmitter, and re-enter the pool of synaptic vesicles available for neurotransmitter release (Heuser and Reese 1973). Thus, a complete understanding of neurotransmitter release requires an explanation not only for how vesicles fuse, but also for how they are able to efficiently progress through this entire exocytosis/endocytosis cycle.