Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia

Ezrin/radixin/moesin (ERM) proteins cross-link actin filaments to plasma membranes to integrate the function of cortical layers, especially microvilli. We found that in cochlear and vestibular sensory hair cells of adult wildtype mice, radixin was specifically enriched in stereocilia, specially developed giant microvilli, and that radixin-deficient (Rdx(-/-)) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset (similar to2 wk), in the cochlea and vestibule of Rdx(-/-) mice, stereocilia developed normally in which ezrin was concentrated. As these Rdx(-/-) mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx(-/-) mice. Thus, we concluded that radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once developed. In Rdx(-/-) mice, ezrin appeared to compensate for radixin deficiency in terms of the development of cochlear stereocilia and the development/maintenance of vestibular stereocilia. These findings indicated the existence of complicate functional redundancy in situ among ERM proteins.