Platelet-collagen interaction: is GPVI the central receptor?
At sites of vascular injury, platelets come into contact with subendothelial collagen, which triggers their activation and the formation of a hemostatic plug. Besides glycoprotein Ib (GPIb) and alphaIIbbeta3 integrin, which indirectly interact with collagen via von Willebrand factor (VWF), several collagen receptors have been identified on platelets, most notably alpha2beta1 integrin and the immunoglobulin (Ig) superfamily member GPVI. Within the last few years, major advances have been made in understanding platelet-collagen interactions including the molecular cloning of GPVI, the generation of mouse strains lacking individual collagen receptors, and the development of collagen receptor-specific antibodies and synthetic peptides. It is now recognized that platelet adhesion to collagen requires prior activation of integrins through "inside-out" signals generated by GPVI and reinforced by released second-wave mediators adenosine diphosphate (ADP) and thromboxane A2. These developments have led to revision of the original "2-site, 2-step" model, which now places GPVI in a central position in the complex processes of platelet tethering, activation, adhesion, aggregation, degranulation, and procoagulant activity on collagen. This review discusses these recent developments and proposes possible mechanisms for how GPVI acts in concert with other receptors and signaling pathways to initiate hemostasis and arterial thrombosis.
Nieswandt
Bernhard
B
Department of Vascular Biology, Rudolf Virchow Center for Experimental Biomedicine Versbacher, Würzburg, Germany. bernhard.nieswandt@virchow.uni-wuerzburg.de
Watson
Steve P
SP
D000244:Adenosine Diphosphate / Q000502:physiology; D000818:Animals; D003001:Cloning, Molecular; D003094:Collagen / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D038982:Integrin alpha2beta1 / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D038981:Receptors, Collagen / Q000378:metabolism*; D015398:Signal Transduction; D013927:Thrombosis / Q000503:physiopathology; D013928:Thromboxane A2 / Q000502:physiology
D038982:Integrin alpha2beta1; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D020033:Protein Isoforms; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen