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Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets.

cam.issuedOnline2018-07-03
cam.orpheus.successThu Jan 30 10:54:24 GMT 2020 - The item has an open VoR version.
dc.contributor.authorWei, Hao
dc.contributor.authorMalcor, Jean-Daniel M
dc.contributor.authorHarper, Matthew T
dc.contributor.orcidHarper, Matthew [0000-0002-4740-637X]
dc.date.accessioned2018-09-20T12:05:27Z
dc.date.available2018-09-20T12:05:27Z
dc.date.issued2018-07-03
dc.description.abstractPlatelets protect the vascular system during damage or inflammation, but platelet activation can result in pathological thrombosis. Activated platelets release a variety of extracellular vesicles (EVs). EVs shed from the plasma membrane often expose phosphatidylserine (PS). These EVs are pro-thrombotic and increased in number in many cardiovascular and metabolic diseases. The mechanisms by which PS-exposing EVs are shed from activated platelets are not well characterised. Cholesterol-rich lipid rafts provide a platform for coordinating signalling through receptors and Ca2+ channels in platelets. We show that cholesterol depletion with methyl-β-cyclodextrin or sequestration with filipin prevented the Ca2+-triggered release of PS-exposing EVs. Although calpain activity was required for release of PS-exposing, calpain-dependent cleavage of talin was not affected by cholesterol depletion. P2Y12 and TPα, receptors for ADP and thromboxane A2, respectively, have been reported to be in platelet lipid rafts. However, the P2Y12 antagonist, AR-C69931MX, or the cyclooxygenase inhibitor, aspirin, had no effect on A23187-induced release of PS-exposing EVs. Together, these data show that lipid rafts are required for release of PS-exposing EVs from platelets.
dc.description.sponsorshipIsaac Newton Trust/ Wellcome Trust ISSF/University of Cambridge Joint Research Grant British Heart Foundation grant SP/15/7/31561
dc.format.mediumElectronic
dc.identifier.doi10.17863/CAM.27871
dc.identifier.eissn2045-2322
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280501
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41598-018-28363-4
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBlood Coagulation
dc.subjectBlood Platelets
dc.subjectCalcimycin
dc.subjectExtracellular Vesicles
dc.subjectFilipin
dc.subjectHealthy Volunteers
dc.subjectHumans
dc.subjectMembrane Microdomains
dc.subjectMembrane Proteins
dc.subjectPhosphatidylserines
dc.subjectPlatelet Activation
dc.subjectSignal Transduction
dc.subjectThrombin
dc.subjectbeta-Cyclodextrins
dc.titleLipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets.
dc.typeArticle
dcterms.dateAccepted2018-06-21
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameSci Rep
prism.startingPage9987
prism.volume8
pubs.funder-project-idBritish Heart Foundation (SP/15/7/31561)
rioxxterms.licenseref.startdate2018-07-03
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionofrecord10.1038/s41598-018-28363-4

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