ArticleeLife2025
Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Multi-omics analysis of ion channels expressed by chicken embryo vestibular type I and type II hair cells.Experimental physiology · 2026Article
- Rescue of stereocilia architecture and hearing function by AAV-CIB2 and AAV-CIB3 in a mouse model of recessive deafness DFNB48.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Integrating AI and Molecular Modeling for Structural Prediction of a Closed-Pore State of the hERG Channel.Journal of chemical information and modeling · 2026Article
- A brief guideline for the studies of structure-function relationship of ion channels using AlphaFold3.Fundamental research · 2026Review
- Evolutionary tuning of an auditory transduction channel.Current biology : CB · 2026Article
- Compensatory Interplay Between Clarin-1 and Clarin-2 Deafness-Associated Proteins Governs Phenotypic Variability in Hearing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The protocadherin-15-LHFPL5 tip link complex is a heterotetrameric assembly in hair cell stereocilia.Biophysical journal · 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
- Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells.The Journal of physiology · 2025Article
- Research Progress on MET, Tip Link, and Stereocilia Complex with Special Reference to Zebrafish.International journal of molecular sciences · 2025Review
- TMC1 and TMC2 are cholesterol-dependent scramblases that regulate membrane homeostasis in auditory hair cells.bioRxiv : the preprint server for biology · 2025Article
- Groove architecture controls lipid scrambling in simulations of protein and model systems.bioRxiv : the preprint server for biology · 2025Article
- Identification of druggable binding sites and small molecules as modulators of TMC1.Communications biology · 2025Article
- Ankyrins are dispensable for mechanotransduction by cochlear hair cells.Hearing research · 2025Article
- CIB2 function is distinct from that of whirlin in the organization of sterocilia architecture.Disease models & mechanisms · 2025Article
- The Diverse Functions of the Calcium- and Integrin-Binding Protein Family.International journal of molecular sciences · 2025Review
- Structural insights into calcium-dependent CIB2-TMC1 interaction in hair cell mechanotransduction.Communications biology · 2025Article
- Anoctamin-1 is a core component of a mechanosensory anion channel complex in C. elegans.Nature communications · 2025Article
- KbioRxiv : the preprint server for biology · 2025Article
- Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.eLife · 2025Article
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17 authors.
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Abstract
Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line. Our AlphaFold 2 models suggest that vertebrate CIB proteins can simultaneously interact with at least two cytoplasmic domains of TMC1 and TMC2 as validated using nuclear magnetic resonance spectroscopy of TMC1 fragments interacting with CIB2 and CIB3. Molecular dynamics simulations of TMC1/2 complexes with CIB2/3 predict that TMCs are structurally stabilized by CIB proteins to form cation channels. Overall, our work demonstrates that intact CIB2/3 and TMC1/2 complexes are integral to hair-cell MET function in vertebrate mechanosensory epithelia.
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