Department of Neurology, University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA.
Neuron. 2011 Aug 11;71(3):474-87. doi: 10.1016/j.neuron.2011.06.010.
Synaptic vesicles belong to two distinct pools, a recycling pool responsible for the evoked release of neurotransmitter and a resting pool unresponsive to stimulation. The uniform appearance of synaptic vesicles has suggested that differences in location or cytoskeletal association account for these differences in function. We now find that the v-SNARE tetanus toxin-insensitive vesicle-associated membrane protein (VAMP7) differs from other synaptic vesicle proteins in its distribution to the two pools, providing evidence that they differ in molecular composition. We also find that both resting and recycling pools undergo spontaneous release, and when activated by deletion of the longin domain, VAMP7 influences the properties of release. Further, the endocytosis that follows evoked and spontaneous release differs in mechanism, and specific sequences confer targeting to the different vesicle pools. The results suggest that different endocytic mechanisms generate synaptic vesicles with different proteins that can endow the vesicles with distinct properties.
突触囊泡属于两个不同的池，一个是负责诱发神经递质释放的再循环池，另一个是对刺激无反应的静息池。突触囊泡的均匀外观表明，位置或细胞骨架的差异导致了这些功能上的差异。我们现在发现，破伤风毒素不敏感的突触小泡相关膜蛋白（VAMP7）在其分布到两个池中与其他突触囊泡蛋白不同，这为它们在分子组成上的差异提供了证据。我们还发现，静息池和再循环池都会自发释放，并且当通过删除长链结构域而被激活时，VAMP7 会影响释放的特性。此外，诱发和自发释放后的内吞作用在机制上不同，并且特定序列将其靶向到不同的囊泡池中。结果表明，不同的内吞作用机制产生了具有不同蛋白质的突触囊泡，这些蛋白质可以赋予囊泡不同的特性。
