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 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 ( approximately 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.
Kitajiri
Shin-ichiro
S
Department of Cell Biology, Kyoto University Faculty of Medicine, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
Fukumoto
Kanehisa
K
Hata
Masaki
M
Sasaki
Hiroyuki
H
Katsuno
Tatsuya
T
Nakagawa
Takayuki
T
Ito
Juichi
J
Tsukita
Shoichiro
S
Tsukita
Sachiko
S
D000818:Animals; D001798:Blood Proteins / Q000235:genetics* / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002923:Cilia / Q000473:pathology*; D003051:Cochlea / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D003638:Deafness / Q000235:genetics*; D006198:Hair Cells, Auditory / Q000648:ultrastructure; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008871:Microvilli / Q000235:genetics; D009154:Mutation; D010750:Phosphoproteins / Q000502:physiology; D013997:Time Factors; D000099149:Ezrin
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D000099149:Ezrin; C071776:radixin