ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers.
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188 citing papers in PubMed, 297 citations in OpenAlex.
- Molecular identity of the mechanotransduction machinery in inner ear hair cells and mechanotransduction-linked hearing loss.Fundamental research · 2026Review
- Cryo-EM reveals a right-handed double-helix dimer architecture of PCDH15.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Overlapping expression and co-operative function of the zebrafish pcdh15 paralogs.Communications biology · 2026Article
- ATP8B1-TMEM30B Flippase Activity Maintains Stereocilia Lipid Asymmetry Required for Hearing.bioRxiv : the preprint server for biology · 2026Article
- LHFPL5 is required for maximal activation of the mechanotransduction channel in cochlear hair cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- Research Progress on MET, Tip Link, and Stereocilia Complex with Special Reference to Zebrafish.International journal of molecular sciences · 2025Review
- Role of Pcdh15 in the development of intrinsic polarity of inner ear hair cells.PLoS genetics · 2025Article
- Identification of druggable binding sites and small molecules as modulators of TMC1.Communications biology · 2025Article
- Cdh23 Gene Mutation-Induced Vestibular Dysfunction in Mice: Abnormal Stereocilia Bundle and Otolith Development and Activation of p53/FoxO Signaling Pathway.Journal of molecular neuroscience : MN · 2025Article
- Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.eLife · 2025Article
- MYO7A is required for the functional integrity of the mechanoelectrical transduction complex in hair cells of the adult cochlea.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Outcomes of cochlear implants in patients withFrontiers in genetics · 2025Article
- The Role of Calcium Signaling in Sensorineural Hearing Loss.International journal of medical sciences · 2025Review
- LOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission.Nature communications · 2024Article
- Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.bioRxiv : the preprint server for biology · 2024Article
- Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.bioRxiv : the preprint server for biology · 2024Article
- Disruption ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- LOXHD1 is indispensable for coupling auditory mechanosensitive channels to the site of force transmission.Research square · 2024Article
- Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
128 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the top of a shorter stereocilium with the lateral membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a hitherto unidentified antigen specifically associated with the tip and kinocilial links of sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to be expressed in the mouse inner ear, and these define four major isoform classes, two with entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing isoform classes reveal that each has a different spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms are distributed in a manner compatible for association with the tip-link complex. An isoform located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and may be an integral component of this structure and/or required for its formation.
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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.