ArticleThe Journal of biological chemistry2013
Dual mechanism of integrin αIIbβ3 closure in procoagulant platelets.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 112 citations in OpenAlex.
- High Prevalence of Acquired Platelet Secretion Defects in Multiple Myeloma.Hamostaseologie · 2026Article
- Temporal phosphoproteomics reveals key regulators of procoagulant COAT platelet generation.Blood vessels, thrombosis & hemostasis · 2026Article
- Procoagulant platelets: linking coagulation and thromboinflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Hemostasis-Sparing Antiplatelet Therapy: Current Concepts and Emerging Targets in Arterial Thrombosis.Biomolecules & therapeutics · 2026Review
- Review
- When the victim becomes the villain: Platelets as drivers of immune dysregulation in ITP.Journal of translational autoimmunity · 2025Review
- Are Procoagulant Platelets an Emerging Therapeutic Target? A General Review with an Emphasis on Their Clinical Significance in Companion Animals.International journal of molecular sciences · 2025Review
- Inter-platelet communication driving thrombus formation is regulated by extracellular calpain-1 cleavage of connexin 62.Haematologica · 2025Article
- Article
- Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Article
- Advances in our understanding of anti-PF4 related immunothrombosis.Frontiers in immunology · 2025Review
- Platelet Activation Pathways Controlling Reversible Integrin αIIbβ3 Activation.TH open : companion journal to thrombosis and haemostasis · 2024Article
- Study on the Mechanism of the Adrenaline-Evoked Procoagulant Response in Human Platelets.International journal of molecular sciences · 2024Article
- Mitofusin-2 Regulates Platelet Mitochondria and Function.Circulation research · 2024Article
- A novel technique to characterize procoagulant platelet formation and evaluate platelet procoagulant tendency in cats by flow cytometry.Frontiers in veterinary science · 2024Article
- Article
- Breakthrough infections after COVID-19 vaccinations do not elicit platelet hyperactivation and are associated with high platelet-lymphocyte and low platelet-neutrophil aggregates.Research and practice in thrombosis and haemostasis · 2023Article
- Platelet procoagulant membrane dynamics: a key distinction between thrombosis and hemostasis?Blood advances · 2023Article
- Platelet-Derived Extracellular Vesicles in Arterial Thrombosis.Advances in experimental medicine and biology · 2023Article
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundInactivation of integrin αIIbβ3 reverses platelet aggregate formation upon coagulation. RESULTS AND
conclusionPlatelets from patient (Scott) and mouse (Capn1(-/-) and Ppif(-/-)) blood reveal a dual mechanism of αIIbβ3 inactivation: by calpain-2 cleavage of integrin-associated proteins and by cyclophilin D/TMEM16F-dependent phospholipid scrambling. SIGNIFICANCE: These data provide novel insight into the switch mechanisms from aggregating to procoagulant platelets. Aggregation of platelets via activated integrin αIIbβ3 is a prerequisite for thrombus formation. Phosphatidylserine-exposing platelets with a key role in the coagulation process disconnect from a thrombus by integrin inactivation via an unknown mechanism. Here we show that αIIbβ3 inactivation in procoagulant platelets relies on a sustained high intracellular Ca(2+), stimulating intracellular cleavage of the β3 chain, talin, and Src kinase. Inhibition of calpain activity abolished protein cleavage, but only partly suppressed αIIbβ3 inactivation. Integrin αIIbβ3 inactivation was unchanged in platelets from Capn1(-/-) mice, suggesting a role of the calpain-2 isoform. Scott syndrome platelets, lacking the transmembrane protein TMEM16F and having low phosphatidylserine exposure, displayed reduced αIIbβ3 inactivation with the remaining activity fully dependent on calpain. In platelets from Ppif(-/-) mice, lacking mitochondrial permeability transition pore (mPTP) formation, agonist-induced phosphatidylserine exposure and αIIbβ3 inactivation were reduced. Treatment of human platelets with cyclosporin A gave a similar phenotype. Together, these data point to a dual mechanism of αIIbβ3 inactivation via calpain(-2) cleavage of integrin-associated proteins and via TMEM16F-dependent phospholipid scrambling with an assistant role of mPTP formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.