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PMID: 19633555 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Review

Tip links in hair cells: molecular composition and role in hearing loss.

Current opinion in otolaryngology & head and neck surgery ·Vol. 17 ·No. 5 ·2009-10-00 ·Pages 388-93

Sakaguchi H, Tokita J, Müller U, Kachar B

Abstract

Tip links are thought to be an essential element of the mechanoelectrical transduction (MET) apparatus in sensory hair cells of the inner ear. The molecules that form tip links have recently been identified, and the analysis of their properties has not only changed our view of MET but also suggests that tip-link defects can cause hearing loss. Structural, histological and biochemical studies show that the extracellular domains of two deafness-associated cadherins, cadherin 23 (CDH23) and protocadherin 15 (PCDH15), interact in trans to form the upper and lower part of each tip link, respectively. High-speed Ca imaging suggests that MET channels are localized exclusively at the lower end of each tip link. Biochemical and genetic studies provide evidence that defects in tip links cause hearing impairment in humans. The identification of the proteins that form tip links have shed new light on the molecular basis of MET and the mechanisms causing hereditary deafness, noise-induced hearing loss and presbycusis.

MeSH Terms
Animals Cadherin Related Proteins Cadherins/metabolism Deafness/genetics Hair Cells, Auditory/cytology,metabolism Hair Cells, Auditory, Inner/metabolism,physiology Hearing Loss, Noise-Induced/genetics Humans Mechanotransduction, Cellular/physiology Mice Presbycusis/genetics Protein Precursors/metabolism
Chemicals
CDH23 protein, human CDHR15 protein, mouse CDHR15, human Cadherin Related Proteins Cadherins Cdh23 protein, mouse Protein Precursors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sakaguchi Hirofumi
Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tokita Joshua
Müller Ulrich
Kachar Bechara
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Article Info
Journal
Current opinion in otolaryngology & head and neck surgery
Abbr.
Curr Opin Otolaryngol Head Neck Surg
ISSN
1531-6998
DOI
10.1097/MOO.0b013e3283303472
Published
2009-10-00
Pages
388-93
Language
English
Region
United States
NLM ID
9417024
PMCID
PMC2921850
Subset
IM
Grants
Intramural NIH HHS · ZIA DC000002-21 · United States
External Links
PubMed source DOI: 10.1097/MOO.0b013e3283303472 PMC Full Text View journal details
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