Cadherin 23 is a component of the tip link in hair-cell stereocilia

Abstract

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 balance; 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 loss. Furthermore, CDH23 is large enough to be the tip link, the extracellular filament proposed to gate the mechanotransduction channel. 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 apparatus, suggesting that CDH23 and myosin-1c cooperate to regulate the activity of mechanically gated ion channels in hair cells.

Alpha-synuclein deficiency and efferent nerve degeneration in the mouse cochlea: A possible cause of early-onset presbycusis

“…They are homozygous for the defective cdh23 ahl allele of the gene encoding cadherin 23, which is a constituent of hair cell stereocilia. Accordingly, one may expect that hearing loss in C57 mice is dependent upon the degeneration of stereocilia (Johnson et al, 1997;Siemens et al, 2004). However, progressive loss of hair cells, degeneration of afferent neurons, the stria vascularis, and even the spiral ligament have all been observed in the C57 mouse strain; these signs are consistent with several of the major types of ARHL suggested by Schuknecht and Gacek (1993).…”

Three-dimensional Architecture of Hair-bundle Linkages Revealed by Electron-microscopic Tomography

“…The divergence of an auxiliary link from the main tip link may underlie the forking of tip links (Furness and Hackney 1985;Kachar et al 2000), for both filaments in the main link connect to the membrane surface. In our projection images, as well as in published micrographs (Zhao et al 1996;Siemens et al 2004), the sides of stereocilia often display globular extracellular densities that may reflect detached auxiliary links.…”

Ameliorative Effects of Exposing DBA/2J Mice to an Augmented Acoustic Environment on Histological Changes in the Cochlea and Anteroventral Cochlear Nucleus

“…Cdh23 is expressed primarily during development, but expression has been detected in adult hair cell stereocilia (Di Palma et al 2001), and Cdh23 was proposed as the tip link (Siemens et al 2004). Thus, one aspect of hearing loss in D2 and B6 mice is likely to involve disruption of stereocilia.…”