Bassoon and the synaptic ribbon organize Ca²+ channels and vesicles to add release sites and promote refilling.

Bassoon and the synaptic ribbon organize Ca²+ channels and vesicles to add release sites and promote refilling.
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DOI:
10.1016/j.neuron.2010.10.027
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发表时间:
2010-11-18
期刊:
影响因子:
16.2
通讯作者:
Moser, Tobias
Moser, Tobias
中科院分区:
医学1区
文献类型:
--
作者:
Frank, Thomas;Rutherford, Mark A.;Strenzke, Nicola;Neef, Andreas;Pangrsic, Tina;Khimich, Darina;Fetjova, Anna;Gundelfinger, Eckart D.;Liberman, M. Charles;Harke, Benjamin;Bryan, Keith E.;Lee, Amy;Egner, Alexander;Riedel, Dietmar;Moser, Tobias

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在突触前活动区,Ca 2+内流触发突触囊泡的融合。目前尚不清楚Ca 2+通道聚集和突触小泡对接是如何组织的。在这里,我们研究的结构和功能的毛细胞带状突触遗传破坏后的突触前支架蛋白巴松。突变的突触-大多缺乏丝带-表现出膜近端囊泡减少,无丝带突触比有丝带的突触受影响更大。Ca 2+通道在突变突触中也较少,并出现在形状异常的簇中。在突变体和野生型突触中,丝带缺失减少了Ca 2+通道数量。快速和持续的胞吐减少,尽管其余的Ca 2+通道的胞吐正常耦合。体外记录显示囊泡补充轻微受损。体内数据的机制建模独立地支持形态学和功能性体外研究结果。我们的结论是,大管和丝带(1)创造了大量的释放网站,通过组织钙通道和囊泡,(2)促进囊泡补充。
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 were 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.
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