Evidence map›Paper›PMID 38388853›Full record

ArticleNature cell biology2024

Drosophila TMEM63 and mouse TMEM63A are lysosomal mechanosensory ion channels.

Kai Li, Yanmeng Guo, Yayu Wang, Ruijun Zhu, Wei Chen, Tong Cheng, Xiaofan Zhang, Yinjun Jia, Ting Liu, Wei Zhang and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
14.4field-weighted citation impact, top 1% of its field
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

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
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  8. Network-Associated Mechanotransduction in Health and Disease.Results and problems in cell differentiation · 2026
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  9. Article
  10. Article
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  17. TMEM63A, associated with hypomyelinating leukodystrophies, is an evolutionarily conserved regulator of myelination.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Kai Li *Department of Physiology, University of California at San Francisco, San Francisco, CA, USA.
Yanmeng Guo *Department of Physiology, University of California at San Francisco, San Francisco, CA, USA.
Yayu Wang *Department of Physiology, University of California at San Francisco, San Francisco, CA, USA.
Ruijun ZhuDepartment of Physiology, University of California at San Francisco, San Francisco, CA, USA.
Wei ChenDepartment of Physiology, University of California at San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6579-0301
Tong ChengDepartment of Physiology, University of California at San Francisco, San Francisco, CA, USA.
Xiaofan ZhangDepartment of Physiology, University of California at San Francisco, San Francisco, CA, USA.
Yinjun JiaSchool of Life Sciences, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.
Ting LiuSchool of Life Sciences, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.
Wei ZhangSchool of Life Sciences, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.ORCID 0000-0002-1648-3364
Lily Yeh JanDepartment of Physiology, University of California at San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3938-8498
Yuh Nung JanDepartment of Physiology, University of California at San Francisco, San Francisco, CA, USA. yuhnung.jan@ucsf.edu.ORCID 0000-0003-1367-6299
Howard Hughes Medical Institute · USCenter for Life Sciences · CN

Funding

Dendrite morphogenesis, function and regenerationR35NS097227 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAN, YUH NUNG · 2017 to 2024
$5.1M
The TMEM16 Family of Ion Channels and Lipid ScramblasesR35NS122110 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LILY JAN · 2021 to 2026
$3.2M
NINDS NIH HHS R35 NS097227NINDS NIH HHS R35 NS122110
6 · The paper itself

Abstract

Cells sense physical forces and convert them into electrical or chemical signals, a process known as mechanotransduction. Whereas extensive studies focus on mechanotransduction at the plasma membrane, little is known about whether and how intracellular organelles sense mechanical force and the physiological functions of organellar mechanosensing. Here we identify the Drosophila TMEM63 (DmTMEM63) ion channel as an intrinsic mechanosensor of the lysosome, a major degradative organelle. Endogenous DmTMEM63 proteins localize to lysosomes, mediate lysosomal mechanosensitivity and modulate lysosomal morphology and function. Tmem63 mutant flies exhibit impaired lysosomal degradation, synaptic loss, progressive motor deficits and early death, with some of these mutant phenotypes recapitulating symptoms of TMEM63-associated human diseases. Importantly, mouse TMEM63A mediates lysosomal mechanosensitivity in Neuro-2a cells, indicative of functional conservation in mammals. Our findings reveal DmTMEM63 channel function in lysosomes and its physiological roles in vivo and provide a molecular basis to explore the mechanosensitive process in subcellular organelles.

Indexed as

DrosophilaMechanotransduction, CellularAnimalsDrosophila ProteinsHumansIon ChannelsLysosomesMammalsMembrane ProteinsMiceDrosophila ProteinsIon ChannelsMembrane ProteinsTmem63 protein, DrosophilaTmem64 protein, mouse

Identifiers

PMID38388853
PMCPMC10940159
OpenAlexW4392049924

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.