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Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets
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-thrombo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030044/ https://www.ncbi.nlm.nih.gov/pubmed/29968812 http://dx.doi.org/10.1038/s41598-018-28363-4 |
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author | Wei, Hao Malcor, Jean-Daniel M. Harper, Matthew T. |
author_facet | Wei, Hao Malcor, Jean-Daniel M. Harper, Matthew T. |
author_sort | Wei, Hao |
collection | PubMed |
description | 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 Ca(2+) channels in platelets. We show that cholesterol depletion with methyl-β-cyclodextrin or sequestration with filipin prevented the Ca(2+)-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. P2Y(12) and TPα, receptors for ADP and thromboxane A(2), respectively, have been reported to be in platelet lipid rafts. However, the P2Y(12) 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. |
format | Online Article Text |
id | pubmed-6030044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60300442018-07-11 Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets Wei, Hao Malcor, Jean-Daniel M. Harper, Matthew T. Sci Rep Article 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 Ca(2+) channels in platelets. We show that cholesterol depletion with methyl-β-cyclodextrin or sequestration with filipin prevented the Ca(2+)-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. P2Y(12) and TPα, receptors for ADP and thromboxane A(2), respectively, have been reported to be in platelet lipid rafts. However, the P2Y(12) 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. Nature Publishing Group UK 2018-07-03 /pmc/articles/PMC6030044/ /pubmed/29968812 http://dx.doi.org/10.1038/s41598-018-28363-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wei, Hao Malcor, Jean-Daniel M. Harper, Matthew T. Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets |
title | Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets |
title_full | Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets |
title_fullStr | Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets |
title_full_unstemmed | Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets |
title_short | Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets |
title_sort | lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030044/ https://www.ncbi.nlm.nih.gov/pubmed/29968812 http://dx.doi.org/10.1038/s41598-018-28363-4 |
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