Evidence map›Paper›PMID 34710431›Full record

ArticleJournal of lipid research2021

Membrane cholesterol regulates TRPV4 function, cytoskeletal expression, and the cellular response to tension.

Monika Lakk, Grace F Hoffmann, Aruna Gorusupudi, Eric Enyong, Amy Lin, Paul S Bernstein, Trine Toft-Bertelsen, Nanna MacAulay, Michael H Elliott, David Križaj

Open access · goldAbstract read
In one paragraph

Article in Journal of lipid research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

38 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Forty sites of TRP channel regulation.Current opinion in chemical biology · 2025
    Review
  15. Review
  16. Systematic review:Frontiers in medicine · 2025
    Review
  17. Mechanobiology in the eye.npj biological physics and mechanics · 2025
    Review
  18. Article
  19. Article
  20. TRPV4 and chloride channels mediate volume sensing in trabecular meshwork cells.American journal of physiology. Cell physiology · 2024
    Article
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

10 authors at 3 institutions in 2 countries.

Monika LakkDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
Grace F HoffmannDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
Aruna GorusupudiDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
Eric EnyongDean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Amy LinDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
Paul S BernsteinDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
Trine Toft-BertelsenDepartment of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
Nanna MacAulayDepartment of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
Michael H ElliottDean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
David KrižajDepartment of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT, USA; Department of Neurobiology, University of Utah, Salt Lake City, UT, USA. Electronic address: david.krizaj@hsc.utah.edu.
University of Utah · USDean McGee Eye Institute · USUniversity of Copenhagen · DK

Funding

Utah Center for Clinical and Translational ScienceUL1TR002538 · NCATS · UNIVERSITY OF UTAH · PI HESS, RACHEL, MAJERSIK, JENNIFER JUHL · 2018 to 2022
$26.0M
University of Utah, Core Vision Research GrantP30EY014800 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Bryan William Jones · 2005 to 2026
$14.6M
P30-CENTER CORE GRANT FOR VISION RESEARCHP30EY021725 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Michelle C Callegan, MICHAEL H ELLIOTT · 2011 to 2026
$10.5M
Biochemistry and Pharmacology of the Macular CarotenoidsR01EY011600 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI BERNSTEIN, PAUL STEVEN · 2004 to 2025
$7.7M
Caveolae-Based Mechanosensors for Conventional Outflow RegulationR01EY028608 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI MICHAEL H ELLIOTT, W Daniel Stamer · 2018 to 2026
$3.8M
Replacement of the Flexcell Tension systemR01EY027920 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI DAVID KRIZAJ · 2017 to 2026
$3.5M
Vision Research Training Grant at the University of UtahT32EY024234 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI DAVID KRIZAJ, Monica L Vetter · 2014 to 2026
$2.3M
Cellular and Molecular Mechanisms that Contribute to Pressure-Induced Retinal Inflammation and PathologyR01EY031817 · NEI · UNIVERSITY OF UTAH · PI KRIZAJ, DAVID · 2021 to 2024
$1.5M
NCATS NIH HHS UL1 TR002538NEI NIH HHS P30 EY014800NEI NIH HHS P30 EY021725NEI NIH HHS R01 EY011600NEI NIH HHS R01 EY027920NEI NIH HHS R01 EY028608NEI NIH HHS R01 EY031817NEI NIH HHS T32 EY024234
6 · The paper itself

Abstract

Despite the association of cholesterol with debilitating pressure-related diseases such as glaucoma, heart disease, and diabetes, its role in mechanotransduction is not well understood. We investigated the relationship between mechanical strain, free membrane cholesterol, actin cytoskeleton, and the stretch-activated transient receptor potential vanilloid isoform 4 (TRPV4) channel in human trabecular meshwork (TM) cells. Physiological levels of cyclic stretch resulted in time-dependent decreases in membrane cholesterol/phosphatidylcholine ratio and upregulation of stress fibers. Depleting free membrane cholesterol with m-β-cyclodextrin (MβCD) augmented TRPV4 activation by the agonist GSK1016790A, swelling and strain, with the effects reversed by cholesterol supplementation. MβCD increased membrane expression of TRPV4, caveolin-1, and flotillin. TRPV4 did not colocalize or interact with caveolae or lipid rafts, apart from a truncated ∼75 kDa variant partially precipitated by a caveolin-1 antibody. MβCD induced currents in TRPV4-expressing Xenopus laevis oocytes. Thus, membrane cholesterol regulates trabecular transduction of mechanical information, with TRPV4 channels mainly located outside the cholesterol-enriched membrane domains. Moreover, the biomechanical milieu itself shapes the lipid content of TM membranes. Diet, cholesterol metabolism, and mechanical stress might modulate the conventional outflow pathway and intraocular pressure in glaucoma and diabetes in part by modulating TM mechanosensing.

Indexed as

AgedAnimalsCell MembraneCells, CulturedCholesterolCytoskeletonHumansMaleMechanotransduction, CellularTRPV Cation ChannelsXenopus laevisCholesterolTRPV4 protein, humanTRPV Cation Channelscell signalingcyclodextrinsdyslipidemiaseye/retinaglaucomalipid raftsmechanotransductionsmooth muscle cellsTRPV4

Identifiers

PMID34710431
PMCPMC8633027
OpenAlexW3210970320

What OpenQuestion holds

Textmetadata
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.