Deák Ferenc, Schoch Susanne, Liu Xinran, Südhof Thomas C, Kavalali Ege T
Center for Basic Neuroscience, Howard Hughes Medical Institute, USA.
Nat Cell Biol. 2004 Nov;6(11):1102-8. doi: 10.1038/ncb1185. Epub 2004 Oct 10.
Synaptobrevin-2 (VAMP-2), the major SNARE protein of synaptic vesicles, is required for fast calcium-triggered synaptic-vesicle exocytosis. Here we show that synaptobrevin-2 is also essential for fast synaptic-vesicle endocytosis. We demonstrate that after depletion of the readily releasable vesicle pool, replenishment of the pool is delayed by knockout of synaptobrevin. This delay was not from a loss of vesicles, because the total number of pre-synaptic vesicles, docked vesicles and actively recycling vesicles was unaffected. However, altered shape and size of the vesicles in synaptobrevin-deficient synapses suggests a defect in endocytosis. Consistent with such a defect, the stimulus-dependent endocytosis of horseradish peroxidase and fluorescent FM1-43 were delayed, indicating that fast vesicle endocytosis may normally be nucleated by a SNARE-dependent coat. Thus, synaptobrevin is essential for two fast synapse-specific membrane trafficking reactions: fast exocytosis for neurotransmitter release and fast endocytosis that mediates rapid reuse of synaptic vesicles.
突触小泡主要的SNARE蛋白突触结合蛋白-2（VAMP-2）是快速钙触发的突触小泡胞吐作用所必需的。在此我们表明，突触结合蛋白-2对于快速的突触小泡内吞作用也是必不可少的。我们证明，在易释放囊泡池耗尽后，突触结合蛋白基因敲除会延迟该池的补充。这种延迟并非由于囊泡丢失，因为突触前囊泡、停靠囊泡和活跃循环囊泡的总数未受影响。然而，突触结合蛋白缺陷型突触中囊泡形状和大小的改变提示内吞作用存在缺陷。与这种缺陷一致，辣根过氧化物酶和荧光FM1-43的刺激依赖性内吞作用延迟，表明快速囊泡内吞作用通常可能由SNARE依赖性衣被引发。因此，突触结合蛋白对于两种快速的突触特异性膜转运反应至关重要：用于神经递质释放的快速胞吐作用以及介导突触小泡快速再利用的快速内吞作用。
