ArticleProceedings of the National Academy of Sciences of the United States of America2019
Elasticity of individual protocadherin 15 molecules implicates tip links as the gating springs for hearing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. 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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42 citing papers in PubMed, 69 citations in OpenAlex.
- 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
- Nonlinear stiffness of NompC gating spring and its implication in mechanotransduction.Science advances · 2026Article
- Cadherin-23 mutations cause calcium-dependent, allele-sensitive mechanosensory defects.iScience · 2026Article
- Hair cell loss - cause or consequence of hearing loss?Frontiers in cell and developmental biology · 2026Review
- Ankyrins are dispensable for mechanotransduction by cochlear hair cells.Hearing research · 2025Article
- NOMPC ion channel hinge forms a gating spring that initiates mechanosensation.Nature neuroscience · 2025Article
- Exploring force-driven stochastic folding dynamics in mechano-responsive proteins and implications in phenotypic variation.Nature communications · 2025Article
- Gating-spring stiffness increases outer-hair-cell bundle stiffness, damping, and receptor current.Scientific reports · 2024Article
- Neural control and innate self-tuning of the hair cell's active process.Biophysical journal · 2024Article
- Nanomechanics of wild-type and mutant dimers of the inner-ear tip-link protein protocadherin 15.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.bioRxiv : the preprint server for biology · 2024Article
- Emergence of slip-ideal-slip behavior in tip-links serve as force filters of sound in hearing.Nature communications · 2024Article
- Nanomechanics of wild-type and mutant dimers of the tip-link protein protocadherin 15.bioRxiv : the preprint server for biology · 2023Article
- Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles.eLife · 2022Article
- cAMP and voltage modulate rat auditory mechanotransduction by decreasing the stiffness of gating springs.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanotransduction in mammalian sensory hair cells.Molecular and cellular neurosciences · 2022Review
- Article
- Usher syndrome type 1-associated gene, pcdh15b, is required for photoreceptor structural integrity in zebrafish.Disease models & mechanisms · 2021Article
- Hearing loss genes reveal patterns of adaptive evolution at the coding and non-coding levels in mammals.BMC biology · 2021Article
- Spontaneous otoacoustic emissions are biomarkers for mice with tectorial membrane defects.Hearing research · 2021Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Hair cells, the sensory receptors of the inner ear, respond to mechanical forces originating from sounds and accelerations. An essential feature of each hair cell is an array of filamentous tip links, consisting of the proteins protocadherin 15 (PCDH15) and cadherin 23 (CDH23), whose tension is thought to directly gate the cell's transduction channels. These links are considered far too stiff to represent the gating springs that convert hair bundle displacement into forces capable of opening the channels, and no mechanism has been suggested through which tip-link stiffness could be varied to accommodate hair cells of distinct frequency sensitivity in different receptor organs and animals. Consequently, the gating spring's identity and mechanism of operation remain central questions in sensory neuroscience. Using a high-precision optical trap, we show that an individual monomer of PCDH15 acts as an entropic spring that is much softer than its enthalpic stiffness alone would suggest. This low stiffness implies that the protein is a significant part of the gating spring that controls a hair cell's transduction channels. The tip link's entropic nature then allows for stiffness control through modulation of its tension. We find that a PCDH15 molecule is unstable under tension and exhibits a rich variety of reversible unfolding events that are augmented when the Ca
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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.