ArticleProceedings of the National Academy of Sciences of the United States of America2013
Characterization of platelet aminophospholipid externalization reveals fatty acids as molecular determinants that regulate coagulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 90 citations in OpenAlex.
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- Altered platelet lipidome in bleeding patients with unexplained platelet function defects.Haematologica · 2026Article
- Membrane asymmetry facilitates murine norovirus entry and persistent enteric infection.PLoS biology · 2025Article
- Activation dynamics study of trapped platelets using a lab-built optical tweezers micro-raman spectrometer.Scientific reports · 2025Article
- Pro-Coagulant Lipids in Physiological Ratios Found in the Activated Platelet Membrane Do Not Impact Clot Structure or Fibrinolysis in Purified Assays.Journal of blood medicine · 2025Article
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- Serum lipidome reveals lipid metabolic dysregulation in severe fever with thrombocytopenia syndrome.BMC medicine · 2024Article
- CaInternational journal of molecular sciences · 2024Review
- Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma.Stem cell research & therapy · 2024Article
- Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease.Journal of lipid research · 2024Article
- Integrin-Dependent Transient Density Increase in Detergent-Resistant Membrane Rafts in Platelets Activated by Thrombin.Biomedicines · 2023Article
- Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.International journal of molecular sciences · 2023Review
- The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses.Journal of lipid research · 2022Article
- The role of procoagulant phospholipids on the surface of circulating blood cells in thrombosis and haemostasis.Open biology · 2022Review
- Shear-Mediated Platelet Activation is Accompanied by Unique Alterations in Platelet Release of Lipids.Cellular and molecular bioengineering · 2021Article
- Lipids and Antiplatelet Therapy: Important Considerations and Future Perspectives.International journal of molecular sciences · 2021Review
- NOD2 deficiency increases retrograde transport of secretory IgA complexes in Crohn's disease.Nature communications · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Aminophospholipid (APL) trafficking across the plasma membrane is a key event in cell activation, apoptosis, and aging and is required for clearance of dying cells and coagulation. Currently the phospholipid molecular species externalized are unknown. Using a lipidomic method, we show that thrombin, collagen, or ionophore-activated human platelets externalize two phosphatidylserines (PSs) and five phosphatidylethanolamines (PEs). Four percent of the total cellular PE/PS pool (∼300 ng/2 × 10(8) cells, thrombin), is externalized via calcium mobilization and protease-activated receptors-1 and -4, and 48% is contained in microparticles. Apoptosis and energy depletion (aging) externalized the same APLs in a calcium-dependent manner, and all stimuli externalized oxidized phospholipids, termed hydroxyeicosatetraenoic acid-PEs. Transmembrane protein-16F (TMEM-16F), the protein mutated in Scott syndrome, was required for PE/PS externalization during thrombin activation and energy depletion, but not apoptosis. Platelet-specific APLs optimally supported tissue factor-dependent coagulation in human plasma, vs. APL with longer or shorter fatty acyl chains. This finding demonstrates fatty acids as molecular determinants of APL that regulate hemostasis. Thus, the molecular species of externalized APL during platelet activation, apoptosis, and energy depletion were characterized, and their ability to support coagulation revealed. The findings have therapeutic implications for bleeding disorders and transfusion therapy. The assay could be applied to other cell events characterized by APL externalization, including cell division and vesiculation.
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