Mechanoelectrical transduction, the conversion of mechanical force into electrochemical signals, underlies a range of sensory phenomena, including touch, hearing and balance. Hair cells of the vertebrate inner ear are specialized mechanosensors that transduce mechanical forces arising from sound waves and head movement to provide our senses of hearing and balance1,2; however, the mechanotransduction channel of hair cells and the molecules that regulate channel activity have remained elusive. One molecule that might participate in mechanoelectrical transduction is cadherin 23 (CDH23), as mutations in its gene cause deafness and age-related hearing loss3,4,5,6. Furthermore, CDH23 is large enough to be the tip link, the extracellular filament proposed to gate the mechanotransduction channel7. Here we show that antibodies against CDH23 label the tip link, and that CDH23 has biochemical properties similar to those of the tip link. Moreover, CDH23 forms a complex with myosin-1c, the only known component of the mechanotransduction apparatus8, suggesting that CDH23 and myosin-1c cooperate to regulate the activity of mechanically gated ion channels in hair cells.
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We thank R. Kemler for E-cadherin clones; M. Senften for L929 cells expressing E-cadherin; T. Hasson, B. Ranscht and H. C. VanSteenhouse for technical advice; and A. Kralli, L. Stowers and A. Patapoutian for critical reading of the manuscript. J.S. was supported by a fellowship from the Boehringer Ingelheim Fonds; A.R. by a C. J. Martin Fellowship from the National Health and Medical Research Council (Australia). This work was supported by grants from the NIDCD and NEI (U.M, P.G.G. and D.S.W.).
The authors declare that they have no competing financial interests.
Characterization of CDH23 antibodies. (JPG 41 kb)
Characterization of CDH23 antibodies. (JPG 23 kb)
Electron micrograph of the kinocilium and adjacent stereocilia of a bullfrog hair cell. (JPG 144 kb)
CDH23 expressing cell lines. (JPG 31 kb)
Colocalization of IL2R-CDH23 with MYO1C in COS cells. (JPG 47 kb)
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