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

@article{Siemens2004Cadherin2I,
  title={Cadherin 23 is a component of the tip link in hair-cell stereocilia},
  author={Jan Siemens and Concepci{\'o}n Lillo and Rachel A Dumont and A Reynolds and David S Williams and Peter G. Gillespie and Ulrich M{\"u}ller},
  journal={Nature},
  year={2004},
  volume={428},
  pages={950-955}
}
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… Expand
Sensory systems: Linking cadherin to hearing
  • H. Wood
  • Biology
  • Nature Reviews Neuroscience
  • 2004
TLDR
The authors examined the hair cells in the sputnik mutant, and they found that the stereocilia were frequently splayed out rather than bundled together, which has important ramifications for the understanding of the inner ear’s mechanotransduction mechanism. Expand
Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells
TLDR
The studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15. Expand
Nanomechanics of tip-link cadherins
TLDR
The results show a remarkable case of functional adaptation of a protein’s nanomechanics to extremely low Ca2+ concentrations and pave the way to a full understanding of the mechanotransduction mechanism mediated by auditory cadherins. Expand
TMHS Is an Integral Component of the Mechanotransduction Machinery of Cochlear Hair Cells
TLDR
It is shown that mechanotransduction is impaired in mice lacking the tetraspan TMHS, which resembles other ion channel regulatory subunits such as the transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor regulatory proteins (TARPs) of AMPA receptors that facilitate channel transport and regulate the properties of pore-forming channel subunits. Expand
Beyond Cell-Cell Adhesion: Sensational Cadherins for Hearing and Balance.
TLDR
The elasticity of tip links and models that bridge the gap between the nanomechanics of cadherins and the micromechanics of hair-cell bundles during inner-ear mechanotransduction are discussed. Expand
Cadherins and mechanotransduction by hair cells.
  • U. Müller
  • Biology, Medicine
  • Current opinion in cell biology
  • 2008
TLDR
These studies show that cadherin 23 (CDH23) and protocadherin 15 (PCDH15) form several of the extracellular filaments that connect the stereocilia and kinocilium of a hair cell into a bundle. Expand
The Dynamic Strength of the Hair-Cell Tip Link Reveals Mechanisms of Hearing and Deafness
TLDR
The dynamics of the tip-link connection are described at single-molecule resolution and it is shown how avidity conferred by its double stranded architecture enhances mechanical strength and lifetime, yet still enables it to act as a dynamic mechanical circuit breaker. Expand
The Mechanotransduction Machinery of Hair Cells
TLDR
Components of the mechanotransduction machinery in hair cells have been identified and several are encoded by genes linked to deafness in humans, which indicates that defects in the mechanosynthesis machinery are the underlying cause of some forms of hearing impairment. Expand
Unraveling cadherin 23's role in development and mechanotransduction
TLDR
The molecular identity of the tip link has been hotly debated by the hair-cell field, and the article by Schwander et al. in this issue of PNAS provides a significant step toward a final settlement of this issue. Expand
Development and Regeneration of Sensory Transduction in Auditory Hair Cells Requires Functional Interaction Between Cadherin-23 and Protocadherin-15
TLDR
Direct evidence is provided implicating CDH23 and PCDH15 proteins in the formation of tip links during development and regeneration of mechanotransduction and tip-link formation in mouse cochleas. Expand
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References

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Mutations in cadherin 23 affect tip links in zebrafish sensory hair cells
TLDR
It is concluded that zebrafish Cdh23 protein is an essential tip link component required for hair-cell mechanotransduction. Expand
Tip-link integrity and mechanical transduction in vertebrate hair cells
TLDR
The involvement of tip links in the transduction process is tested by treating bundles with a BAPTA-buffered, low-Ca2+ saline (10(-9) M). Expand
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TLDR
The cloning of disease genes and studies of model organisms have provided insights into the mechanisms that regulate the differentiation of hair cells and their cytoskeleton, and the function of receptors such as integrins and protocadherins, and cytoplasmic proteins such as Rho-type GTPases and unconventional myosins, in organizing the actin cytos skeleton. Expand
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The development of ideas on mechanotransduction in acousticolateral hair cells is described, leading to the current idea that transduction depends on deflection of the bundle of stereocilia by aExpand
Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle
TLDR
It is proposed that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia. Expand
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TLDR
Supporting the equivalence of tip links with gating springs, mechanoelectrical transduction returns over the same time period as tip links; strikingly, adaptation is substantially reduced, even 24 hr after breaking tip links. Expand
Identification of a 120 kd hair-bundle myosin located near stereociliary tips
TLDR
To provide direct evidence for the presence of myosin isozymes in hair bundles, photoaffinity labeling with vanadate-trapped uridine and adenine nucleotides was used to identify proteins of 120, 160, and 230 kd in a preparation of hair bundles purified from the bullfrog's sacculus. Expand
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TLDR
The specific localization of myosin-Iβ at both ends of tip links supports its role as the adaptation motor of mechanoelectrical transduction in vertebrate hair cells. Expand
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TLDR
The structure of the tip link suggests that it is either a helical polymer or a braided pair of filamentous macromolecules and is thus likely to be relatively stiff and inextensible, incompatible with the measured elasticity of the gating spring. Expand
A Novel Antigen Sensitive to Calcium Chelation That is Associated with the Tip Links and Kinocilial Links of Sensory Hair Bundles
TLDR
Results provide the first identification of a cell surface antigen associated with tip links, indicate that tip links share properties in common with kinocilial links, and reveal a second epitope that is common to both sensory hair bundles and the ciliary calyx of photoreceptors. Expand
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