ArticleCell reports2023
The tetraspan LHFPL5 is critical to establish maximal force sensitivity of the mechanotransduction channel of cochlear hair cells.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- PIPbioRxiv : the preprint server for biology · 2026Article
- 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
- Tonotopic specialization of MYO7A isoforms in auditory hair cells.Nature communications · 2026Article
- Exome sequencing identifies known and candidate genes in hearing impairment in Cameroon.Communications medicine · 2026Article
- The protocadherin-15-LHFPL5 tip link complex is a heterotetrameric assembly in hair cell stereocilia.Biophysical journal · 2026Article
- LHFPL5 splice site variant in a cat with deafness and vestibular dysfunction.Animal genetics · 2025Article
- 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
- Ankyrins are dispensable for mechanotransduction by cochlear hair cells.Hearing research · 2025Article
- Ectopic mouse TMC1 and TMC2 alone form mechanosensitive channels that are potently modulated by TMIE.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Diverse Functions of the Calcium- and Integrin-Binding Protein Family.International journal of molecular sciences · 2025Review
- Inhibition of GABARAP or GABARAPL1 prevents aminoglycoside- induced hearing loss.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.eLife · 2025Article
- 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
- LOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission.Nature communications · 2024Article
- Sequence variations and accessory proteins adapt TMC functions to distinct sensory modalities.Neuron · 2024Article
- Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.bioRxiv : the preprint server for biology · 2024Article
- Sensory transduction in auditory hair cells-PIEZOs can't touch this.The Journal of general physiology · 2024Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The mechanoelectrical transduction (MET) channel of cochlear hair cells is gated by the tip link, but the mechanisms that establish the exquisite force sensitivity of this MET channel are not known. Here, we show that the tetraspan lipoma HMGIC fusion partner-like 5 (LHFPL5) directly couples the tip link to the MET channel. Disruption of these interactions severely perturbs MET. Notably, the N-terminal cytoplasmic domain of LHFPL5 binds to an amphipathic helix in TMC1, a critical gating domain conserved between different MET channels. Mutations in the amphipathic helix of TMC1 or in the N-terminus of LHFPL5 that perturb interactions of LHFPL5 with the amphipathic helix affect channel responses to mechanical force. We conclude that LHFPL5 couples the tip link to the MET channel and that channel gating depends on a structural element in TMC1 that is evolutionarily conserved between MET channels. Overall, our findings support a tether model for transduction channel gating by the tip link.
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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.