Evidence map›Paper›PMID 31184584›Full record

ArticleeLife2019

Mouse TRPA1 function and membrane localization are modulated by direct interactions with cholesterol.

Justyna B Startek, Brett Boonen, Alejandro López-Requena, Ariel Talavera, Yeranddy A Alpizar, Debapriya Ghosh, Nele Van Ranst, Bernd Nilius, Thomas Voets, Karel Talavera

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

33 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
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  9. Article
  10. Regulation of ThermoTRP Channels by PIP2 and Cholesterol.Advances in experimental medicine and biology · 2023
    Article
  11. Potent Activation of Human but Not Mouse TRPA1 by JT010.International journal of molecular sciences · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Membrane Interactivity of Capsaicin Antagonized by Capsazepine.International journal of molecular sciences · 2022
    Article
  16. TRPA1 Expression and Pathophysiology in Immune Cells.International journal of molecular sciences · 2021
    Review
  17. Activation ofInternational journal of molecular sciences · 2021
    Article
  18. Cyclodextrins increase membrane tension and are universal activators of mechanosensitive channels.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Review
  20. The Form and Function of PIEZO2.Annual review of biochemistry · 2021
    Review
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 2 institutions in 1 country.

Justyna B StartekLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID 0000-0003-1131-1149
Brett BoonenLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID 0000-0002-5026-3963
Alejandro López-RequenaLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Ariel TalaveraCenter for Microscopy and Molecular Imaging (CMMI), Laboratory of Microscopy, Université Libre de Bruxelles, Gosselies, Belgium.
Yeranddy A AlpizarLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID 0000-0003-1959-5393
Debapriya GhoshLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Nele Van RanstLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Bernd NiliusLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Thomas VoetsLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID 0000-0001-5526-5821
Karel TalaveraLaboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID 0000-0002-3124-138X
VIB-KU Leuven Center for Brain & Disease Research · BEUniversité Libre de Bruxelles · BE

Funding

FWO G070212NFWO G0C7715NFWO G0D0417NFWO Postdoctoral FellowshipResearch Council KU Leuven C14/18/086Research Council KU Leuven GOA/14/11Research Foundation Flanders G070212NResearch Foundation Flanders G0C7715NResearch Foundation Flanders G0D0417NResearch Foundation Flanders Postdoctoral Fellowship
6 · The paper itself

Abstract

The cation channel TRPA1 transduces a myriad of noxious chemical stimuli into nociceptor electrical excitation and neuropeptide release, leading to pain and neurogenic inflammation. Despite emergent evidence that TRPA1 is regulated by the membrane environment, it remains unknown whether this channel localizes in membrane microdomains or whether it interacts with cholesterol. Using total internal reflection fluorescence microscopy and density gradient centrifugation we found that mouse TRPA1 localizes preferably into cholesterol-rich domains and functional experiments revealed that cholesterol depletion decreases channel sensitivity to chemical agonists. Moreover, we identified two structural motifs in transmembrane segments 2 and 4 involved in mTRPA1-cholesterol interactions that are necessary for normal agonist sensitivity and plasma membrane localization. We discuss the impact of such interactions on TRPA1 gating mechanisms, regulation by the lipid environment, and role of this channel in sensory membrane microdomains, all of which helps to understand the puzzling pharmacology and pathophysiology of this channel.

Indexed as

Amino Acid SequenceAnimalsCell MembraneCHO CellsCholesterolCricetinaeCricetulusHEK293 CellsHumansLuminescent ProteinsMembrane MicrodomainsMiceMicroscopy, FluorescenceModels, MolecularProtein BindingProtein DomainsCholesterolLuminescent ProteinsRed Fluorescent ProteinTRPA1 Cation Channelbiochemistrychemical biologychemosensationcholesterolCRAC motiflipid raftmouseneurosciencesensory neuronTRPA1

Identifiers

PMID31184584
PMCPMC6590989
OpenAlexW2950772078

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.