The mechanosensory transduction machinery in inner ear hair cells

W Zheng, JR Holt - Annual review of biophysics, 2021 - annualreviews.org
Annual review of biophysics, 2021annualreviews.org
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 …
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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