CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells.
CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells.
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DOI：
10.1038/s41467-017-00061-1
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发表时间：
2017-06-29
影响因子：
16.6
通讯作者：
Ahmed ZM
中科院分区：
文献类型：
--
作者：
Giese APJ;Tang YQ;Sinha GP;Bowl MR;Goldring AC;Parker A;Freeman MJ;Brown SDM;Riazuddin S;Fettiplace R;Schafer WR;Frolenkov GI;Ahmed ZM
内耳毛细胞通过静纤毛的偏转来检测声音，静纤毛是排列成高低梯度的行的微绒毛样突起。钙和整合素结合蛋白2是听力所必需的，定位于静纤毛，但其确切功能尚不清楚。在这里，我们的特点是两个突变的小鼠品系，一个缺乏钙和整合素结合蛋白2和一个携带人类肥胖相关的Cib 2突变，并表明，这两个都是耳聋，表现出没有mechanotransduction在听觉毛细胞，尽管存在的提示链接门的mechanotransducer通道。此外，机械转导短列静纤毛过度生长在毛细胞束的Cib2突变体。此外，我们报告说，钙和整合素结合蛋白2结合到毛细胞机械转导复合物，TMC 1和TMC 2的组件，这些相互作用被破坏的致敏Cib 2突变。我们得出结论，钙和整合素结合蛋白2是所需的正常运作的mechanotransducer通道，并参与限制的增长转导静纤毛。内耳毛细胞通过静纤毛的偏转来检测声音，静纤毛具有机械门控通道。在这里，作者表明，负责Usher综合征的蛋白质CIB 2与这些通道相互作用，并且对它们的功能和小鼠的听力至关重要。
Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows of graded heights. Calcium and integrin-binding protein 2 is essential for hearing and localizes to stereocilia, but its exact function is unknown. Here, we have characterized two mutant mouse lines, one lacking calcium and integrin-binding protein 2 and one carrying a human deafness-related Cib2 mutation, and show that both are deaf and exhibit no mechanotransduction in auditory hair cells, despite the presence of tip links that gate the mechanotransducer channels. In addition, mechanotransducing shorter row stereocilia overgrow in hair cell bundles of both Cib2 mutants. Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia. Inner ear hair cells detect sound through deflection of stereocilia that harbor mechanically-gated channels. Here the authors show that protein responsible for Usher syndrome, CIB2, interacts with these channels and is essential for their function and hearing in mice.