Cadherin 23 is a component of the tip link in hair-cell stereocilia.
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.
Siemens
Jan
J
The Scripps Research Institute, Department of Cell Biology, Institute for Childhood and Neglected Disease, La Jolla, California 92037, USA.
Lillo
Concepcion
C
Dumont
Rachel A
RA
Reynolds
Anna
A
Williams
David S
DS
Gillespie
Peter G
PG
Müller
Ulrich
U
D017398:Alternative Splicing; D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D007758:Ear, Inner / Q000378:metabolism / Q000648:ultrastructure; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000648:ultrastructure; D006309:Hearing / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D040542:Mechanotransduction, Cellular; D051379:Mice; D024461:Myosin Type I; D009218:Myosins / Q000378:metabolism; D011898:Ranidae
C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; C499091:Cdh23 protein, mouse; C470422:Myo1c protein, mouse; D024461:Myosin Type I; D009218:Myosins