毛细胞中的纤毛连接：分子组成及其在听力损失中的作用。
Tip links in hair cells: molecular composition and role in hearing loss.
作者信息
Sakaguchi Hirofumi, Tokita Joshua, Müller Ulrich, Kachar Bechara
机构信息
Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
出版信息
Curr Opin Otolaryngol Head Neck Surg. 2009 Oct;17(5):388-93. doi: 10.1097/MOO.0b013e3283303472.
Abstract
PURPOSE OF REVIEW
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.
RECENT FINDINGS
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 Ca 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.
SUMMARY
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.
摘要
综述目的
纤毛顶端连接被认为是内耳感觉毛细胞机械电转导（MET）装置的一个基本要素。最近已鉴定出构成纤毛顶端连接的分子，对其特性的分析不仅改变了我们对MET的看法，还表明纤毛顶端连接缺陷可导致听力损失。
最新发现
结构、组织学和生化研究表明，两种与耳聋相关的钙黏蛋白，钙黏蛋白23（CDH23）和原钙黏蛋白15（PCDH15）的细胞外结构域相互反式作用，分别形成每个纤毛顶端连接的上部和下部。高速钙成像表明，MET通道仅定位在每个纤毛顶端连接的下端。生化和遗传学研究提供了证据，证明纤毛顶端连接缺陷会导致人类听力障碍。
总结
构成纤毛顶端连接的蛋白质的鉴定为MET的分子基础以及导致遗传性耳聋、噪声性听力损失和老年性耳聋的机制提供了新的线索。
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