The Mechanosensory Transduction Machinery in Inner Ear Hair Cells.

The Mechanosensory Transduction Machinery in Inner Ear Hair Cells.
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DOI:
10.1146/annurev-biophys-062420-081842
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发表时间:
2021-05-06
影响因子:
12.4
通讯作者:
Holt JR
Holt JR
中科院分区:
生物学1区
文献类型:
--
作者:
Zheng W;Holt JR

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声音诱导的机械刺激是通过内耳高度特化的毛细胞中的精细机械感觉转导(MT)机制来检测的。在过去的几十年中,遗传性耳聋的遗传学研究已经发现了MT复合物的几种分子成分,并且围绕孔形成亚基的分子身份进行了激烈的争论。MT组件如何响应物理刺激而一致地起作用还不完全清楚。在这篇综述中,我们总结并讨论了多条支持跨膜通道样1是一个长期寻找的MT通道亚基这一假设的证据。我们还审查了MT复合物的其他成分的具体作用,包括原钙粘蛋白15,钙粘蛋白23,脂肪瘤HMGIC融合伴侣样5,跨膜内耳,钙和整合素结合家族成员2,和锚蛋白。基于这些最新进展,我们提出了一个统一的毛细胞MT理论,可以调和迄今为止获得的大部分功能发现。最后,我们讨论了在分子和原子水平上全面了解毛细胞MT需要解决的关键问题。
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.
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