Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
EMBO Rep. 2018 Nov;19(11). doi: 10.15252/embr.201744937. Epub 2018 Sep 10.
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 (, ) 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 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.
传入内毛细胞突触含有突触小带，它确保了囊泡的持续供应。突触小泡（SVs）排列在形态上可分辨的池中，通过细丝与小带或突触前膜相连。我们提出，细丝在小带处的 SV 再供应和胞吐中起主要作用。使用先进的电子显微镜，我们证明 SVs 是由每个囊泡的细丝数量及其连接来定义的亚池组织的。在刺激下，SVs 越来越多地与其他囊泡和小带相连，而在膜上则以单连接的 SVs 为主。毛细胞蛋白 otoferlin（otoferlin）的突变小鼠耳聋严重，持续释放减少，可作为研究 IHCs 中 SV 补充的模型。在刺激下，由于停靠下游的损伤，多连接和停靠的囊泡（在野生型中很少观察到）在活性区积累。总之，细丝将囊泡在小带型活性区组织成亚池，以支持囊泡供应、运输，最终释放。
