ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Development and regeneration of sensory transduction in auditory hair cells requires functional interaction between cadherin-23 and protocadherin-15.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 60 citations in OpenAlex.
- Molecular identity of the mechanotransduction machinery in inner ear hair cells and mechanotransduction-linked hearing loss.Fundamental research · 2026Review
- Article
- Cdhr1a and pcdh15b link photoreceptor outer segments with inner segment calyceal processes revealing a potential mechanism for cone-rod dystrophy.bioRxiv : the preprint server for biology · 2026Article
- Regulation of membrane homeostasis by TMC1 mechanoelectrical transduction channels is essential for hearing.Science advances · 2022Article
- The Mechanosensory Transduction Machinery in Inner Ear Hair Cells.Annual review of biophysics · 2021Review
- Single-molecule force spectroscopy reveals the dynamic strength of the hair-cell tip-link connection.Nature communications · 2021Article
- Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Distinct functions of TMC channels: a comparative overview.Cellular and molecular life sciences : CMLS · 2019Review
- The Development of Cooperative Channels Explains the Maturation of Hair Cell's Mechanotransduction.Biophysical journal · 2019Article
- Function and Dysfunction of TMC Channels in Inner Ear Hair Cells.Cold Spring Harbor perspectives in medicine · 2019Review
- Beyond Cell-Cell Adhesion: Sensational Cadherins for Hearing and Balance.Cold Spring Harbor perspectives in biology · 2018Review
- Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness.Structure (London, England : 1993) · 2018Article
- Integrin α8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells.Journal of cell science · 2017Article
- A Model for Link Pruning to Establish Correctly Polarized and Oriented Tip Links in Hair Bundles.Biophysical journal · 2017Article
- Functional Analysis of the Transmembrane and Cytoplasmic Domains of Pcdh15a in Zebrafish Hair Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Using thermal scanning assays to test protein-protein interactions of inner-ear cadherins.PloS one · 2017Article
- An elastic element in the protocadherin-15 tip link of the inner ear.Nature communications · 2016Article
- Differential effects of Cdh23(753A) on auditory and vestibular functional aging in C57BL/6J mice.Neurobiology of aging · 2016Article
- The elusive mechanotransduction machinery of hair cells.Current opinion in neurobiology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Tip links are extracellular filaments that connect pairs of hair cell stereocilia and convey tension to mechanosensitive channels. Recent evidence suggests that tip links are formed by calcium-dependent interactions between the N-terminal domains of cadherin-23 (CDH23) and protocadherin-15 (PCDH15). Mutations in either CDH23 or PCDH15 cause deafness in mice and humans, indicating the molecules are required for normal inner ear function. However, there is little physiological evidence to support a direct role for CDH23 and PCDH15 in hair cell mechanotransduction. To investigate the contributions of CDH23 and PCDH15 to mechanotransduction and tip-link formation, we examined outer hair cells of mouse cochleas during development and after chemical disruption of tip links. We found that tip links and mechanotransduction with all the qualitative properties of mature transduction recovered within 24 h after disruption. To probe tip-link formation, we measured transduction currents after extracellular application of recombinant CDH23 and PCDH15 fragments, which included putative interaction domains (EC1). Both fragments inhibited development and regeneration of transduction but did not disrupt transduction in mature cells. PCDH15 fragments that carried a mutation in EC1 that causes deafness in humans did not inhibit transduction development or regeneration. Immunolocalization revealed wild-type fragments bound near the tips of hair cell stereocilia. Scanning electron micrographs revealed that hair bundles exposed to fragments had a reduced number of linkages aligned along the morphological axis of sensitivity of the bundle. Together, the data provide direct evidence implicating CDH23 and PCDH15 proteins in the formation of tip links during development and regeneration of mechanotransduction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.