Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcR gamma chain

Platelet glycoprotein (GP) VI has been proposed as the major collagen recep tor for activation of human platelets. Human GPVI belongs to the immunoglob ulin superfamily and is noncovalently associated with the FcR gamma chain t hat is involved in signaling through the receptor. In mice, similar mechani sms seem to exist as platelets from FcR gamma chain-deficient mice do not a ggregate in response to collagen. However, the activating collagen receptor on mouse platelets has not been definitively identified. In the current st udy we examined the function and in vivo expression of GPVI in control and FcR gamma chain-deficient mice with the first monoclonal antibody against G PVI (JAQ1). On wild type platelets, JAQ1 inhibited platelet aggregation ind uced by collagen but not PMA or thrombin. Cross-linking of bound JAQ1, on t he other hand, induced aggregation of wild type but not FcR gamma chain-def icient platelets. JAQ1 stained platelets and megakaryocytes from wild type but not FcR gamma chain-deficient mice. Furthermore, JAQ1 recognized GPVI ( approximately 60 kDa) in immunoprecipitation and Western blot experiments w ith wild type but not FcR gamma chain deficient platelets. These results st rongly suggest that GPVI is the collagen receptor responsible for platelet activation in mice and demonstrate that the association with the FcR gamma chain is critical for its expression and function.