ArticleProceedings of the National Academy of Sciences of the United States of America2020
Deafness mutation D572N of TMC1 destabilizes TMC1 expression by disrupting LHFPL5 binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Molecular identity of the mechanotransduction machinery in inner ear hair cells and mechanotransduction-linked hearing loss.Fundamental research · 2026Review
- 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 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
- Molecular Determinants of TMC Protein Biogenesis and Trafficking.International journal of molecular sciences · 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
- LOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission.Nature communications · 2024Article
- LHFPL5 is a key element in force transmission from the tip link to the hair cell mechanotransducer channel.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- LOXHD1 is indispensable for coupling auditory mechanosensitive channels to the site of force transmission.Research square · 2024Article
- Establishment and analysis of artificial neural network diagnosis model for coagulation-related molecular subgroups in coronary artery disease.Frontiers in genetics · 2024Article
- Single molecule studies of the native hair cell mechanosensory transduction complex.bioRxiv : the preprint server for biology · 2023Article
- Novel autosomal dominant TMC1 variants linked to hearing loss: insight into protein-lipid interactions.BMC medical genomics · 2023Article
- Article
- Mechanoelectrical transduction-related genetic forms of hearing loss.Current opinion in physiology · 2023Article
- The tetraspan LHFPL5 is critical to establish maximal force sensitivity of the mechanotransduction channel of cochlear hair cells.Cell reports · 2023Article
- Multiple plasma membrane reporters discern LHFPL5 region that blocks trafficking to the plasma membrane.Scientific reports · 2023Article
- Review
- The conductance and organization of the TMC1-containing mechanotransducer channel complex in auditory hair cells.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
- POT1-TPP1 binding stabilizes POT1, promoting efficient telomere maintenance.Computational and structural biotechnology journal · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transmembrane channel-like protein 1 (TMC1) and lipoma HMGIC fusion partner-like 5 (LHFPL5) are recognized as two critical components of the mechanotransduction complex in inner-ear hair cells. However, the physical and functional interactions of TMC1 and LHFPL5 remain largely unexplored. We examined the interaction between TMC1 and LHFPL5 by using multiple approaches, including our recently developed ultrasensitive microbead-based single-molecule pulldown (SiMPull) assay. We demonstrate that LHFPL5 physically interacts with and stabilizes TMC1 in both heterologous expression systems and in the soma and hair bundle of hair cells. Moreover, the semidominant deafness mutation D572N in human TMC1 (D569N in mouse TMC1) severely disrupted LHFPL5 binding and destabilized TMC1 expression. Thus, our findings reveal previously unrecognized physical and functional interactions of TMC1 and LHFPL5 and provide insights into the molecular mechanism by which the D572N mutation causes deafness. Notably, these findings identify a missing link in the currently known physical organization of the mechanotransduction macromolecular complex. Furthermore, this study has demonstrated the power of the microbead-based SiMPull assay for biochemical investigation of rare cells such as hair cells.
Indexed as
Identifiers
What OpenQuestion holds
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.