Functional significance of the platelet immune receptors GPVI and CLEC-2
Julie Rayes,1 Steve P. Watson,1,2 and Bernhard Nieswandt3
1Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
2Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, United Kingdom.
3Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
Address correspondence to: Bernhard Nieswandt, Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Centre, University of Würzburg, Josef-Schneider-Str 2, 97080 Würzburg, Germany. Phone: 49.931.31.80405; Email: bernhard.nieswandt@virchow.uni-wuerzburg.de. Or to: Steve P. Watson, Institute of Cardiovascular Sciences, IBR Building, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. Phone: 44.121.4146514, Email: s.p.watson@bham.ac.uk.
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1Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
2Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, United Kingdom.
3Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
Address correspondence to: Bernhard Nieswandt, Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Centre, University of Würzburg, Josef-Schneider-Str 2, 97080 Würzburg, Germany. Phone: 49.931.31.80405; Email: bernhard.nieswandt@virchow.uni-wuerzburg.de. Or to: Steve P. Watson, Institute of Cardiovascular Sciences, IBR Building, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. Phone: 44.121.4146514, Email: s.p.watson@bham.ac.uk.
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Watson, S.
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1Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
2Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, United Kingdom.
3Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
Address correspondence to: Bernhard Nieswandt, Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Centre, University of Würzburg, Josef-Schneider-Str 2, 97080 Würzburg, Germany. Phone: 49.931.31.80405; Email: bernhard.nieswandt@virchow.uni-wuerzburg.de. Or to: Steve P. Watson, Institute of Cardiovascular Sciences, IBR Building, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. Phone: 44.121.4146514, Email: s.p.watson@bham.ac.uk.
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First published January 2, 2019 - More info
J Clin Invest. 2019;129(1):12–23. https://doi.org/10.1172/JCI122955.
Copyright © 2019, American Society for Clinical Investigation
Although platelets are best known for their role in hemostasis, they are also crucial in development, host defense, inflammation, and tissue repair. Many of these roles are regulated by the immune-like receptors glycoprotein VI (GPVI) and C-type lectin receptor 2 (CLEC-2), which signal through an immunoreceptor tyrosine–based activation motif (ITAM). GPVI is activated by collagen in the subendothelial matrix, by fibrin and fibrinogen in the thrombus, and by a remarkable number of other ligands. CLEC-2 is activated by the transmembrane protein podoplanin, which is found outside of the vasculature and is upregulated in development, inflammation, and cancer, but there is also evidence for additional ligands. In this Review, we discuss the physiological and pathological roles of CLEC-2 and GPVI and their potential as targets in thrombosis and thrombo-inflammatory disorders (i.e., disorders in which inflammation plays a critical role in the ensuing thrombosis) relative to current antiplatelet drugs.
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