Zheng Wang, Holt Jeffrey R
Departments of Otolaryngology and Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA; email:
Annu Rev Biophys. 2021 May 6;50:31-51. doi: 10.1146/annurev-biophys-062420-081842. Epub 2020 Dec 7.
Sound-induced mechanical stimuli are detected by elaborate mechanosensory transduction (MT) machinery in highly specialized hair cells of the inner ear. Genetic studies of inherited deafness in the past decades have uncovered several molecular constituents of the MT complex, and intense debate has surrounded the molecular identity of the pore-forming subunits. How the MT components function in concert in response to physical stimulation is not fully understood. In this review, we summarize and discuss multiple lines of evidence supporting the hypothesis that transmembrane channel-like 1 is a long-sought MT channel subunit. We also review specific roles of other components of the MT complex, including protocadherin 15, cadherin 23, lipoma HMGIC fusion partner-like 5, transmembrane inner ear, calcium and integrin-binding family member 2, and ankyrins. Based on these recent advances, we propose a unifying theory of hair cell MT that may reconcile most of the functional discoveries obtained to date. Finally, we discuss key questions that need to be addressed for a comprehensive understanding of hair cell MT at molecular and atomic levels.
声音诱导的机械刺激由内耳高度特化的毛细胞中精密的机械感觉转导（MT）机制检测。过去几十年对遗传性耳聋的遗传学研究揭示了MT复合体的几种分子成分，并且围绕孔形成亚基的分子身份展开了激烈争论。MT成分如何协同响应物理刺激尚不完全清楚。在本综述中，我们总结并讨论了多条证据，这些证据支持跨膜通道样蛋白1是长期寻找的MT通道亚基这一假说。我们还回顾了MT复合体其他成分的具体作用，包括原钙黏蛋白15、钙黏蛋白23、脂肪瘤HMGIC融合伴侣样蛋白5、跨膜内耳、钙和整合素结合家族成员2以及锚蛋白。基于这些最新进展，我们提出了一种毛细胞MT的统一理论，该理论可能调和迄今获得的大多数功能发现。最后，我们讨论了为在分子和原子水平全面理解毛细胞MT需要解决的关键问题。
