Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets.
cam.issuedOnline | 2018-07-03 | |
cam.orpheus.success | Thu Jan 30 10:54:24 GMT 2020 - The item has an open VoR version. | |
dc.contributor.author | Wei, Hao | |
dc.contributor.author | Malcor, Jean-Daniel M | |
dc.contributor.author | Harper, Matthew T | |
dc.contributor.orcid | Harper, Matthew [0000-0002-4740-637X] | |
dc.date.accessioned | 2018-09-20T12:05:27Z | |
dc.date.available | 2018-09-20T12:05:27Z | |
dc.date.issued | 2018-07-03 | |
dc.description.abstract | Platelets 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.sponsorship | Isaac Newton Trust/ Wellcome Trust ISSF/University of Cambridge Joint Research Grant British Heart Foundation grant SP/15/7/31561 | |
dc.format.medium | Electronic | |
dc.identifier.doi | 10.17863/CAM.27871 | |
dc.identifier.eissn | 2045-2322 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/280501 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.publisher.url | http://dx.doi.org/10.1038/s41598-018-28363-4 | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Blood Coagulation | |
dc.subject | Blood Platelets | |
dc.subject | Calcimycin | |
dc.subject | Extracellular Vesicles | |
dc.subject | Filipin | |
dc.subject | Healthy Volunteers | |
dc.subject | Humans | |
dc.subject | Membrane Microdomains | |
dc.subject | Membrane Proteins | |
dc.subject | Phosphatidylserines | |
dc.subject | Platelet Activation | |
dc.subject | Signal Transduction | |
dc.subject | Thrombin | |
dc.subject | beta-Cyclodextrins | |
dc.title | Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets. | |
dc.type | Article | |
dcterms.dateAccepted | 2018-06-21 | |
prism.issueIdentifier | 1 | |
prism.publicationDate | 2018 | |
prism.publicationName | Sci Rep | |
prism.startingPage | 9987 | |
prism.volume | 8 | |
pubs.funder-project-id | British Heart Foundation (SP/15/7/31561) | |
rioxxterms.licenseref.startdate | 2018-07-03 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.type | Journal Article/Review | |
rioxxterms.versionofrecord | 10.1038/s41598-018-28363-4 |
Files
Original bundle
1 - 2 of 2
Loading...
- Name:
- s41598-018-28363-4.pdf
- Size:
- 4.51 MB
- Format:
- Adobe Portable Document Format
- Description:
- Published version
- Licence
- https://creativecommons.org/licenses/by/4.0/
No Thumbnail Available
- Name:
- Lipid rafts accepted manuscript.pdf
- Size:
- 2.84 MB
- Format:
- Adobe Portable Document Format
- Description:
- Accepted version
- Licence
- https://creativecommons.org/licenses/by/4.0/
License bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- DepositLicenceAgreement.pdf
- Size:
- 417.78 KB
- Format:
- Adobe Portable Document Format