Zhang Hong, Qiu Xufeng, Mittelstadt Jonah, Müller Ulrich
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Meicine, Baltimore, MD 21205, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Meicine, Baltimore, MD 21205, USA.
Hear Res. 2025 Apr;459:109224. doi: 10.1016/j.heares.2025.109224. Epub 2025 Mar 1.
The mechanotransduction (MET) channels of cochlear hair cells is a heteromeric protein complex consisting of TMC1, TMIE and CIB2. The activity of this ion channel is thought to be regulated by a gating spring, a mechanical element that conveys sound-induced vibrations to the MET channel. In nematodes, orthologs of TMC-1, TMIE and CIB2 similarly assemble into a MET channel mediating light nose-touch. Studies in nematodes have suggested that nematode Unc-44, an ortholog of the mammalian ankyrins Ank1, 2, and 3, encodes a gating spring that tethers the nematode MET channel to the cytoskeleton. Here we show that mammalian ankyrins are expressed in cochlear hair cells. Using single and triple conditional knockout mice, we demonstrate that Ank1, 2, and 3 are dispensable for the function of cochlear hair cells. We concluded that Ank1, 2, and 3 are unlikely to be components of the gating spring that gates mechanotransduction channels in mammalian cochlear hair cells.
耳蜗毛细胞的机械转导（MET）通道是一种由TMC1、TMIE和CIB2组成的异源蛋白复合体。该离子通道的活性被认为受门控弹簧调节，门控弹簧是一种将声音引起的振动传递给MET通道的机械元件。在线虫中，TMC-1、TMIE和CIB2的直系同源物同样组装成一个介导轻触鼻感觉的MET通道。线虫研究表明，线虫Unc-44是哺乳动物锚蛋白Ank1、2和3的直系同源物，编码一种将门控弹簧与线虫MET通道连接到细胞骨架的蛋白。在这里，我们表明哺乳动物锚蛋白在耳蜗毛细胞中表达。使用单条件和三条件敲除小鼠，我们证明Ank1、2和3对耳蜗毛细胞的功能不是必需的。我们得出结论，Ank1、2和3不太可能是在哺乳动物耳蜗毛细胞中门控机械转导通道的门控弹簧的组成部分。
