Tip links in hair cells: molecular composition and role in hearing loss.
Tip links in hair cells: molecular composition and role in hearing loss.
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DOI：
10.1097/moo.0b013e3283303472
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发表时间：
2009-10
影响因子：
1.6
通讯作者：
Kachar B
中科院分区：
文献类型：
--
作者：
Sakaguchi H;Tokita J;Müller U;Kachar B
耳尖连接被认为是内耳感觉毛细胞中机电转导（MET）装置的重要组成部分。形成尖端连接的分子最近已经被确定，对其性质的分析不仅改变了我们对MET的看法，而且表明尖端连接缺陷可能导致听力损失。结构、组织学和生化研究表明，两种耳聋相关的钙粘蛋白cadherin 23 （CDH23）和原cadherin 15 （PCDH15）的细胞外结构域通过反式相互作用，分别形成每个尖端连接的上部和下部。高速Ca2+成像表明MET通道仅定位于每个尖端连接的下端。生物化学和遗传学研究提供证据表明，尖端连接缺陷导致人类听力损伤。形成尖端连接的蛋白质的鉴定为MET的分子基础和导致遗传性耳聋、噪声性听力损失和老年性耳聋的机制提供了新的线索。
Tip links are thought to be an essential element of the mechanoelectrical transduction (MET) apparatus in sensory hair cells of the inner ear. The molecules that form tip links have recently been identified, and the analysis of their properties has not only changed our view of MET but also suggests that tip link defects can cause hearing loss. Structural, histological and biochemical studies show that the extracellular domains of two deafness-associated cadherins, cadherin 23 (CDH23) and protocadherin 15 (PCDH15), interact in trans to form the upper and lower part of each tip link, respectively. High speed Ca2+ imaging suggests that MET channels are localized exclusively at the lower end of each tip link. Biochemical and genetic studies provide evidence that defects in tip links cause hearing impairment in humans. The identification of the proteins that form tip links have shed new light on the molecular basis of MET and the mechanisms causing hereditary deafness, noise-induced hearing loss and presbycusis.