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PMID: 15057245 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Nature ·Vol. 428 ·No. 6986 ·2004-04-29 ·Pages 950-5

Siemens J, Lillo C, Dumont RA, Reynolds A, Williams DS, Gillespie PG, Müller U

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.

MeSH Terms
Alternative Splicing Animals Cadherin Related Proteins Cadherins/analysis,genetics,metabolism Cell Line Cilia/metabolism,ultrastructure Ear, Inner/metabolism,ultrastructure Hair Cells, Auditory/metabolism,ultrastructure Hearing/physiology Humans Ion Channel Gating Mechanotransduction, Cellular Mice Myosin Type I Myosins/metabolism Ranidae
Chemicals
CDH23 protein, human Cadherin Related Proteins Cadherins Cdh23 protein, mouse Myo1c protein, mouse Myosin Type I Myosins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Siemens Jan
The Scripps Research Institute, Department of Cell Biology, Institute for Childhood and Neglected Disease, La Jolla, California 92037, USA.
Lillo Concepcion
Dumont Rachel A
Reynolds Anna
Williams David S
Gillespie Peter G
Müller Ulrich
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2004-04-29
Epub
2004-00-31
Pages
950-5
Language
English
Region
England
NLM ID
0410462
Subset
IM
Grants
NEI NIH HHS · R01 EY007042 · United States
NEI NIH HHS · R01 EY007042-18 · United States
Corrections
CommentIn
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