InnerEarLab, Department of Otolaryngology and Center for Molecular Physiology of the Brain, University of Göttingen Medical Center, 37099 Göttingen, Germany.
Neuron. 2010 Nov 18;68(4):724-38. doi: 10.1016/j.neuron.2010.10.027.
At the presynaptic active zone, Ca²+ influx triggers fusion of synaptic vesicles. It is not well understood how Ca²+ channel clustering and synaptic vesicle docking are organized. Here, we studied structure and function of hair cell ribbon synapses following genetic disruption of the presynaptic scaffold protein Bassoon. Mutant synapses--mostly lacking the ribbon--showed a reduction in membrane-proximal vesicles, with ribbonless synapses affected more than ribbon-occupied synapses. Ca²+ channels were also fewer at mutant synapses and appeared in abnormally shaped clusters. Ribbon absence reduced Ca²+ channel numbers at mutant and wild-type synapses. Fast and sustained exocytosis was reduced, notwithstanding normal coupling of the remaining Ca²+ channels to exocytosis. In vitro recordings revealed a slight impairment of vesicle replenishment. Mechanistic modeling of the in vivo data independently supported morphological and functional in vitro findings. We conclude that Bassoon and the ribbon (1) create a large number of release sites by organizing Ca²+ channels and vesicles, and (2) promote vesicle replenishment.
在突触前活性区,钙离子内流引发突触小泡融合。钙离子通道簇集和突触小泡对接如何组织尚不清楚。在这里,我们研究了发毛细胞带状突触的结构和功能,这些突触是通过破坏突触前支架蛋白 Bassoon 产生的。突变突触——主要缺乏连接带——表现出膜近端囊泡减少,而无连接带的突触比有连接带的突触受影响更大。钙通道在突变突触中也较少,并且出现异常形状的簇集。连接带缺失减少了突变和野生型突触中的钙通道数量。尽管剩余的钙通道与胞吐作用正常偶联,但快速和持续的胞吐作用减少。体外记录显示囊泡补充略有受损。体内数据的机制建模独立支持了体外形态和功能发现。我们得出结论,Bassoon 和连接带(1)通过组织钙离子通道和囊泡来产生大量的释放位点,并且(2)促进囊泡补充。