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Platelet receptor signaling in thrombus formation

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Abstract

Platelet activation and subsequent thrombus formation at sites of vascular injury is crucial for normal hemostasis, but it can also cause myocardial infarction and stroke. The initial capture of flowing platelets to the injured vessel wall is mediated by the interaction of the glycoprotein (GP) Ib-V-IX complex with von Willebrand factor immobilized on the exposed subendothelial extracellular matrix. Tethered platelets are then able to bind to collagens through the immunoglobulin-like receptor GPVI and to initiate cellular activation, a process that is reinforced by G protein-coupled receptors stimulated by locally produced thrombin and soluble mediators released from activated platelets. These signaling events lead to a rise in the cytosolic Ca2+ concentration, rearrangement of the cytoskeleton, release of granule content, and functional upregulation of integrin adhesion receptors allowing firm adhesion and thrombus growth. Fully activated platelets also undergo a procoagulant conversion thereby facilitating coagulation and thrombus stabilization. This review summarizes the most important receptor systems and signaling mechanisms involved in platelet activation and thrombus formation with special focus on recent discoveries.

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Acknowledgments

Our work cited in this review was supported by the Deutsche Forschungsgemeinschaft (SFB 688 and 487) and the Rudolf Virchow Center. D.S. was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg. We thank Markus Bender and Ina Hagedorn for proofreading the manuscript.

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  1. Chair of Vascular Medicine, University Hospital and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany

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Stegner, D., Nieswandt, B. Platelet receptor signaling in thrombus formation. J Mol Med 89, 109–121 (2011). https://doi.org/10.1007/s00109-010-0691-5

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