Vesicle sub-pool organization at inner hair cell ribbon synapses
Vesicle sub-pool organization at inner hair cell ribbon synapses
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DOI：
10.15252/embr.201744937
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发表时间：
2018-11-01
期刊：
影响因子：
7.7
通讯作者：
Wichmann, Carolin
中科院分区：
文献类型：
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作者：
Chakrabarti, Rituparna;Michanski, Susann;Wichmann, Carolin
传入内毛细胞突触内有突触带，以保证囊泡的持续供应。突触囊泡（SV）排列在形态上可辨别的池中，通过细丝连接到带状物或突触前膜。我们建议，丝在SV再供应和胞吐在丝带中发挥了重要作用。使用先进的电子显微镜，我们表明，SV的组织在子池定义的细丝数量每个囊泡及其连接。刺激后，SV越来越多地连接到其他囊泡和丝带，而单拴系SV占主导地位的膜。毛细胞蛋白otoferlin（pachanga，Otof（Pga/Pga））的突变小鼠严重失聪，持续释放减少，可作为研究IHC SV补充的模型。在刺激后，多栓系和对接囊泡（野生型中很少观察到）积累在奥托夫（Pga/Pga）活性区由于下游的对接损伤。总之，囊泡在带状活性区由细丝组织成子池，以支持囊泡的供应、运输和最终释放。
The afferent inner hair cell synapse harbors the synaptic ribbon, which ensures a constant vesicle supply. Synaptic vesicles (SVs) are arranged in morphologically discernable pools, linked via filaments to the ribbon or the presynaptic membrane. We propose that filaments play a major role in SV resupply and exocytosis at the ribbon. Using advanced electron microscopy, we demonstrate that SVs are organized in sub-pools defined by the filament number per vesicle and its connections. Upon stimulation, SVs increasingly linked to other vesicles and to the ribbon, whereas single-tethered SVs dominated at the membrane. Mutant mice for the hair cell protein otoferlin (pachanga, Otof(Pga/Pga)) are profoundly deaf with reduced sustained release, serving as a model to investigate the SV replenishment at IHCs. Upon stimulation, multiple-tethered and docked vesicles (rarely observed in wild-type) accumulated at Otof(Pga/Pga) active zones due to an impairment downstream of docking. Conclusively, vesicles are organized in sub-pools at ribbon-type active zones by filaments to support vesicle supply, transport, and finally release.