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

Author

Listed:
  • Jan Siemens

    (Institute for Childhood and Neglected Disease)

  • Concepcion Lillo

    (University of California at San Diego)

  • Rachel A. Dumont

    (Oregon Hearing Research Center & Vollum Institute, Oregon Health & Science University
    Vollum Institute, Oregon Health & Science University)

  • Anna Reynolds

    (Institute for Childhood and Neglected Disease)

  • David S. Williams

    (University of California at San Diego)

  • Peter G. Gillespie

    (Oregon Hearing Research Center & Vollum Institute, Oregon Health & Science University
    Vollum Institute, Oregon Health & Science University)

  • Ulrich Müller

    (Institute for Childhood and Neglected Disease)

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 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.

Suggested Citation

  • Jan Siemens & Concepcion Lillo & Rachel A. Dumont & Anna Reynolds & David S. Williams & Peter G. Gillespie & Ulrich Müller, 2004. "Cadherin 23 is a component of the tip link in hair-cell stereocilia," Nature, Nature, vol. 428(6986), pages 950-955, April.
  • Handle: RePEc:nat:nature:v:428:y:2004:i:6986:d:10.1038_nature02483
    DOI: 10.1038/nature02483
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    Cited by:

    1. Pei Wang & Katharine K. Miller & Enqi He & Siddhant S. Dhawan & Christopher L. Cunningham & Nicolas Grillet, 2024. "LOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Jeong Han Lee & Maria C. Perez-Flores & Seojin Park & Hyo Jeong Kim & Yingying Chen & Mincheol Kang & Jennifer Kersigo & Jinsil Choi & Phung N. Thai & Ryan L. Woltz & Dolores Columba Perez-Flores & Gu, 2024. "The Piezo channel is a mechano-sensitive complex component in the mammalian inner ear hair cell," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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