Department of Cell Biology, Emory University, Atlanta, GA 30322.
Department of Otology and Skull Base Surgery, Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
eNeuro. 2023 Jun 5;10(6). doi: 10.1523/ENEURO.0420-22.2023. Print 2023 Jun.
The cochlea hair cells transform mechanic sounds to neural signals with a remarkable sensitivity and resolution. This is achieved via the precisely sculpted mechanotransduction apparatus of the hair cells and the supporting structure of the cochlea. The shaping of the mechanotransduction apparatus, the staircased stereocilia bundles on the apical surface of the hair cells, requires an intricate regulatory network including planar cell polarity (PCP) and primary cilia genes in orienting stereocilia bundles and building molecular machinery of the apical protrusions. The mechanism linking these regulatory components is unknown. Here, we show that a small GTPase known for its role in protein trafficking, Rab11a, is required for ciliogenesis in hair cells during development in mice. In addition, in the absence of Rab11a, stereocilia bundles lost their cohesion and integrity, and mice are deaf. These data indicate an essential role of protein trafficking in the formation of hair cell mechanotransduction apparatus, implicating a role of Rab11a or protein trafficking in linking the cilia and polarity regulatory components with the molecular machinery in building the cohesive and precisely shaped stereocilia bundles.
耳蜗毛细胞将机械声音转化为神经信号，具有惊人的灵敏度和分辨率。这是通过毛细胞的精确雕刻的机械转导装置和耳蜗的支持结构来实现的。机械转导装置的形成，即毛细胞顶表面的阶梯状静纤毛束，需要一个复杂的调节网络，包括平面细胞极性 (PCP) 和初级纤毛基因，以定向静纤毛束并构建顶端突起的分子机制。将这些调节成分联系起来的机制尚不清楚。在这里，我们表明，一种已知在蛋白质运输中起作用的小 GTPase，Rab11a，在小鼠发育过程中毛细胞的纤毛发生中是必需的。此外，在缺乏 Rab11a 的情况下，静纤毛束失去了它们的凝聚性和完整性，而小鼠失聪。这些数据表明蛋白质运输在毛细胞机械转导装置的形成中起着重要作用，暗示 Rab11a 或蛋白质运输在将纤毛和极性调节成分与构建凝聚和精确形状的静纤毛束的分子机制联系起来方面起着作用。
