Cadherin 23 is a component of the tip link in hair-cell stereocilia
Cadherin 23 is a component of the tip link in hair-cell stereocilia
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DOI：
10.1038/nature02483
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发表时间：
2004-04-29
期刊：
影响因子：
64.8
通讯作者：
Müller, U
中科院分区：
文献类型：
--
作者：
Siemens, J;Lillo, C;Müller, U
机电转换，即机械力转化为电化学信号，是一系列感觉现象的基础，包括触觉，听觉和平衡。脊椎动物内耳的毛细胞是专门的机械传感器，它能感知声波和头部运动产生的机械力，为我们提供听觉和平衡感（1，2）;然而，毛细胞的机械转导通道和调节通道活性的分子仍然难以捉摸。可能参与机械电传导的一种分子是钙粘蛋白23（CDH 23），因为其基因突变会导致耳聋和年龄相关性听力损失（3-6）。此外，CDH 23足够大，可以作为尖端连接，细胞外丝被提议用于门控机械转导通道（7）。在这里，我们表明，针对CDH 23的抗体标记的提示链接，并且CDH 23具有类似的生化特性的提示链接。此外，CDH 23与肌球蛋白-1c（机械传导装置的唯一已知成分）形成复合物（8），表明CDH 23和肌球蛋白-1c协同调节毛细胞中机械门控离子通道的活性。
Mechanoelectrical transduction, the conversion of mechanical force into electrochemical signals, underlies a range of sensory phenomena, including touch, hearing and balance. Hair cells of the vertebrate inner ear are specialized mechanosensors that transduce mechanical forces arising from sound waves and head movement to provide our senses of hearing and balance(1,2); however, the mechanotransduction channel of hair cells and the molecules that regulate channel activity have remained elusive. One molecule that might participate in mechanoelectrical transduction is cadherin 23 (CDH23), as mutations in its gene cause deafness and age-related hearing loss(3-6). Furthermore, CDH23 is large enough to be the tip link, the extracellular filament proposed to gate the mechanotransduction channel(7). Here we show that antibodies against CDH23 label the tip link, and that CDH23 has biochemical properties similar to those of the tip link. Moreover, CDH23 forms a complex with myosin-1c, the only known component of the mechanotransduction apparatus(8), suggesting that CDH23 and myosin-1c cooperate to regulate the activity of mechanically gated ion channels in hair cells.