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dc.contributor.authorStartek, Justyna B
dc.contributor.authorBoonen, Brett
dc.contributor.authorLopez-Requena, Alejandro
dc.contributor.authorTalavera, Ariel
dc.contributor.authorAlpizar, Yeranddy A
dc.contributor.authorGhosh, Debapriya
dc.contributor.authorVan Ranst, Nele
dc.contributor.authorNilius, Bernd
dc.contributor.authorVoets, Thomas
dc.contributor.authorTalavera, Karel
dc.date.accessioned2020-01-14T04:32:35Z
dc.date.available2020-01-14T04:32:35Z
dc.date.issued2019
dc.identifier.issn2050-084X
dc.identifier.doi10.7554/eLife.46084
dc.identifier.urihttp://hdl.handle.net/10072/390235
dc.description.abstractThe 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publishereLife Sciences Publications
dc.relation.ispartofjournaleLife
dc.relation.ispartofvolume8
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchcode3101
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiology
dc.subject.keywordsLife Sciences & Biomedicine - Other Topics
dc.subject.keywordsRECEPTOR POTENTIAL A1
dc.titleMouse TRPA1 function and membrane localization are modulated by direct interactions with cholesterol
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationStartek, JB; Boonen, B; Lopez-Requena, A; Talavera, A; Alpizar, YA; Ghosh, D; Van Ranst, N; Nilius, B; Voets, T; Talavera, K, Mouse TRPA1 function and membrane localization are modulated by direct interactions with cholesterol, eLife, 2019, 8
dcterms.dateAccepted2019-06-10
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-01-14T04:29:21Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© Startek et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorNilius, Bernd


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