Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets.
Publication Date
2018-07-03Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
8
Issue
1
Pages
9987
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Wei, H., Malcor, J., & Harper, M. (2018). Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets.. Sci Rep, 8 (1), 9987. https://doi.org/10.1038/s41598-018-28363-4
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.
Keywords
Blood Platelets, Membrane Microdomains, Humans, Filipin, Calcimycin, beta-Cyclodextrins, Thrombin, Phosphatidylserines, Membrane Proteins, Signal Transduction, Blood Coagulation, Platelet Activation, Healthy Volunteers, Extracellular Vesicles
Sponsorship
Isaac Newton Trust/ Wellcome Trust ISSF/University of Cambridge Joint Research Grant
British Heart Foundation grant SP/15/7/31561
Funder references
British Heart Foundation (SP/15/7/31561)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1038/s41598-018-28363-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280501
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