Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia

Abstract

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 wild-type 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 (∼2 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.