ArticleeLife2021
Molecular structures and conformations of protocadherin-15 and its complexes on stereocilia elucidated by cryo-electron tomography.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- 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
- Article
- The protocadherin-15-LHFPL5 tip link complex is a heterotetrameric assembly in hair cell stereocilia.Biophysical journal · 2026Article
- 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
- Inner Ear Organoids: A Hydrogel-Based Platform for Drug Screening and Deafness Modeling.Neuroscience bulletin · 2026Review
- ExoSloNano: multimodal nanogold labels for identification of macromolecules in live cells and cryo-electron tomograms.Nature methods · 2026Article
- Protocadherin 20 Is a POU Class 2 Homeobox 3 Target Gene Required for Proper Tuft Cell Microvillus Organization.Cellular and molecular gastroenterology and hepatology · 2026Article
- Spontaneous calcium transients in hair cell stereocilia.Scientific reports · 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
- Molecular basis of proteolytic cleavage regulation by the extracellular matrix receptor dystroglycan.Structure (London, England : 1993) · 2024Article
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- Article
- Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.bioRxiv : the preprint server for biology · 2024Article
- Single molecule studies of the native hair cell mechanosensory transduction complex.bioRxiv : the preprint server for biology · 2023Article
- The actin cytoskeleton in hair bundle development and hearing loss.Hearing research · 2023Review
- Antiparallel dimer structure of CELSR cadherin in solution revealed by high-speed atomic force microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanosensory transduction (MT), the conversion of mechanical stimuli into electrical signals, underpins hearing and balance and is carried out within hair cells in the inner ear. Hair cells harbor actin-filled stereocilia, arranged in rows of descending heights, where the tips of stereocilia are connected to their taller neighbors by a filament composed of protocadherin 15 (PCDH15) and cadherin 23 (CDH23), deemed the 'tip link.' Tension exerted on the tip link opens an ion channel at the tip of the shorter stereocilia, thus converting mechanical force into an electrical signal. While biochemical and structural studies have provided insights into the molecular composition and structure of isolated portions of the tip link, the architecture, location, and conformational states of intact tip links, on stereocilia, remains unknown. Here, we report in situ cryo-electron microscopy imaging of the tip link in mouse stereocilia. We observe individual PCDH15 molecules at the tip and shaft of stereocilia and determine their stoichiometry, conformational heterogeneity, and their complexes with other filamentous proteins, perhaps including CDH23. The PCDH15 complexes occur in clusters, frequently with more than one copy of PCDH15 at the tip of stereocilia, suggesting that tip links might consist of more than one copy of PCDH15 complexes and, by extension, might include multiple MT complexes.
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Registered trials
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.