Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRgamma chain.
Platelet glycoprotein (GP) VI has been proposed as the major collagen receptor for activation of human platelets. Human GPVI belongs to the immunoglobulin superfamily and is noncovalently associated with the FcRgamma chain that is involved in signaling through the receptor. In mice, similar mechanisms seem to exist as platelets from FcRgamma chain-deficient mice do not aggregate in response to collagen. However, the activating collagen receptor on mouse platelets has not been definitively identified. In the current study we examined the function and in vivo expression of GPVI in control and FcRgamma chain-deficient mice with the first monoclonal antibody against GPVI (JAQ1). On wild type platelets, JAQ1 inhibited platelet aggregation induced by collagen but not PMA or thrombin. Cross-linking of bound JAQ1, on the other hand, induced aggregation of wild type but not FcRgamma chain-deficient platelets. JAQ1 stained platelets and megakaryocytes from wild type but not FcRgamma chain-deficient mice. Furthermore, JAQ1 recognized GPVI (approximately 60 kDa) in immunoprecipitation and Western blot experiments with wild type but not FcRgamma chain-deficient platelets. These results strongly suggest that GPVI is the collagen receptor responsible for platelet activation in mice and demonstrate that the association with the FcRgamma chain is critical for its expression and function.
Nieswandt
B
B
Department of Molecular Oncology, General Surgery, University of Witten-Herdecke, 42283 Wuppertal, Germany. niesand@klinikum-wuppertal.de
Bergmeier
W
W
Schulte
V
V
Rackebrandt
K
K
Gessner
J E
JE
Zirngibl
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology*; D016023:Integrins / Q000378:metabolism*; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010974:Platelet Aggregation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D038981:Receptors, Collagen; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; D017452:Receptors, IgG; C098341:platelet membrane glycoprotein VI; D003094:Collagen