ArticlePLoS biology2013
Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed.
- PIPbioRxiv : the preprint server for biology · 2026Article
- The Impact of Pcdh15 Deficiency on Cellular Energy Metabolism and Oxidative Stress, and Its Role and Mechanism in Hearing Loss.Clinical and experimental otorhinolaryngology · 2026Article
- VASCilia is an open-source, deep learning-based tool for 3D analysis of cochlear hair cell stereocilia bundles.PLoS biology · 2026Article
- Spontaneous calcium transients in hair cell stereocilia.Scientific reports · 2025Article
- VASCilia (Vision Analysis StereoCilia): A Napari Plugin for Deep Learning-Based 3D Analysis of Cochlear Hair Cell Stereocilia Bundles.bioRxiv : the preprint server for biology · 2025Article
- Single-molecule fluorescence microscopy reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of live inner ear hair cells.Nature communications · 2025Article
- Research Progress on MET, Tip Link, and Stereocilia Complex with Special Reference to Zebrafish.International journal of molecular sciences · 2025Review
- PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.Communications biology · 2024Article
- SUB-immunogold-SEM reveals nanoscale distribution of submembranous epitopes.Nature communications · 2024Article
- LOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission.Nature communications · 2024Article
- Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.bioRxiv : the preprint server for biology · 2024Article
- A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment.Antioxidants (Basel, Switzerland) · 2024Review
- PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.bioRxiv : the preprint server for biology · 2024Article
- Disruption ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- SUB-Immunogold-SEM reveals nanoscale distribution of submembranous epitopes.Research square · 2024Article
- LOXHD1 is indispensable for coupling auditory mechanosensitive channels to the site of force transmission.Research square · 2024Article
- TMTC4 is a hair cell-specific human deafness gene.JCI insight · 2023Article
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- Mini-PCDH15 gene therapy rescues hearing in a mouse model of Usher syndrome type 1F.Nature communications · 2023Article
27 more citing papers are in PubMed but not listed here.
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9 authors.
Funding
Abstract
Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at the upper end of the link. In terminally differentiated mammalian auditory hair cells, tip links are subjected to sound-induced forces throughout an organism's life. Although hair cells can regenerate disrupted tip links and restore hearing, the molecular details of this process are unknown. We developed a novel implementation of backscatter electron scanning microscopy to visualize simultaneously immuno-gold particles and stereocilia links, both of only a few nanometers in diameter. We show that functional, mechanotransduction-mediating tip links have at least two molecular compositions, containing either PCDH15/CDH23 or PCDH15/PCDH15. During regeneration, shorter tip links containing nearly equal amounts of PCDH15 at both ends appear first. Whole-cell patch-clamp recordings demonstrate that these transient PCDH15/PCDH15 links mediate mechanotransduction currents of normal amplitude but abnormal Ca(2+)-dependent decay (adaptation). The mature PCDH15/CDH23 tip link composition is re-established later, concomitant with complete recovery of adaptation. Thus, our findings provide a molecular mechanism for regeneration and maintenance of mechanosensory function in postmitotic auditory hair cells and could help identify elusive components of the mechanotransduction machinery.
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