Evidence map›Paper›PMID 39256406›Full record

ArticleNature communications2024

LOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission.

Pei Wang, Katharine K Miller, Enqi He, Siddhant S Dhawan, Christopher L Cunningham, Nicolas Grillet

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Novel SLC26A4 variant in Pendred syndrome with non-classical inheritance: a case report.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025
    Article
  4. 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 · 2025
    Article
  5. [Expert consensus on prognostic evaluation of cochlear implantation in hereditary hearing loss].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025
    Article
  6. Molecular Determinants of TMC Protein Biogenesis and Trafficking.International journal of molecular sciences · 2025
    Article
  7. The Diverse Functions of the Calcium- and Integrin-Binding Protein Family.International journal of molecular sciences · 2025
    Review
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Pei WangDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, 240 Pasteur Drive, Stanford, CA, USA.ORCID 0000-0002-0538-7641
Katharine K MillerDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, 240 Pasteur Drive, Stanford, CA, USA.ORCID 0000-0002-0690-7426
Enqi HeDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, 240 Pasteur Drive, Stanford, CA, USA.
Siddhant S DhawanDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, 240 Pasteur Drive, Stanford, CA, USA.
Christopher L CunninghamPittsburgh Hearing Research Center, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.ORCID 0000-0002-9619-4190
Nicolas GrilletDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, 240 Pasteur Drive, Stanford, CA, USA. ngrillet@stanford.edu.ORCID 0000-0001-8007-9246

Funding

Molecular Genetics of Human Age-Related Hearing LossR01AG081608 · NIA · UNIVERSITY OF KENTUCKY · PI Nicolas Grillet · 2023 to 2026
$2.3M
Function of LOXHD1 in mechanosensory hair cellsR01DC016409 · NIDCD · STANFORD UNIVERSITY · PI GRILLET, NICOLAS · 2018 to 2022
$2.1M
Processing and localization of the mechanotransduction channel subunit TMC1R01DC021835 · NIDCD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CUNNINGHAM, CHRISTOPHER L · 2024 to 2024
$696k
Mechanisms of Protein Assembly and Transport in Hair CellsR21DC019195 · NIDCD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CUNNINGHAM, CHRISTOPHER L · 2021 to 2023
$477k
High-resolution localization of the hair cell mechanotransduction channel components by immunogold-scanning electronic microscopyR21DC019457 · NIDCD · STANFORD UNIVERSITY · PI GRILLET, NICOLAS · 2021 to 2022
$435k
NIA NIH HHS R01 AG081608NIDCD NIH HHS R01 DC016409NIDCD NIH HHS R01 DC021835NIDCD NIH HHS R21 DC019195NIDCD NIH HHS R21 DC019457U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) 1R01AG081608-01U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) 1R01DC016409-01A1U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) 1R01DC021835-01U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) R21DC019195
6 · The paper itself

Abstract

Hair cell bundles consist of stereocilia arranged in rows of increasing heights, connected by tip links that transmit sound-induced forces to shorter stereocilia tips. Auditory mechanotransduction channel complexes, composed of proteins TMC1/2, TMIE, CIB2, and LHFPL5, are located at the tips of shorter stereocilia. While most components can interact with the tip link in vitro, their ability to maintain the channel complexes at the tip link in vivo is uncertain. Return, using mouse models, we show that an additional component, LOXHD1, is essential for keeping TMC1-pore forming subunits at the tip link but is dispensable for TMC2. Using SUB-immunogold-SEM, we showed that TMC1 localizes near the tip link but mislocalizes without LOXHD1. LOXHD1 selectively interacts with TMC1, CIB2, LHFPL5, and tip-link protein PCDH15. Our results demonstrate that TMC1-driven mature auditory channels require LOXHD1 to stay connected to the tip link and remain functional, while TMC2-driven developmental channels do not.

Indexed as

Mechanotransduction, CellularMembrane ProteinsAnimalsCadherin Related ProteinsCadherinsFemaleHair Cells, AuditoryMaleMiceMice, Inbred C57BLMice, KnockoutProtein PrecursorsStereociliaCadherin Related ProteinsCadherinsCDHR15 protein, mouseLHFPL5 protein, mouseMembrane ProteinsProtein PrecursorsTMC1 protein, mouse

Identifiers

PMID39256406
PMCPMC11387651

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Registered trials

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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.