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


RESULTS
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.


CONCLUSIONS
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.
Sakaguchi
Hirofumi
H
Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tokita
Joshua
J
Müller
Ulrich
U
Kachar
Bechara
B
D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000378:metabolism; D003638:Deafness / Q000235:genetics; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism / Q000502:physiology*; D006317:Hearing Loss, Noise-Induced / Q000235:genetics; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D011304:Presbycusis / Q000235:genetics; D011498:Protein Precursors / Q000378:metabolism
C442480:CDH23 protein, human; C418976:CDHR15 protein, mouse; C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; C499091:Cdh23 protein, mouse; D011498:Protein Precursors