Receptor shedding from human platelets. ADAM10 and ADAM17 are responsible for the shedding of platelet-surface receptor ectodomains of GPIbα, GPV, and GPVI. The physiological triggers of ADAM activity dictate the rate and extent of loss of specific receptors. (A) GPVI is stable on resting platelets but rapidly cleaved by ADAM10 on exposure to active factor X (FXa) or fibrin, as well as by brief exposure to elevated fluid shear stress, and collagen binding. (B) The release of glycocalicin from the GPIb-IX complex occurs constitutively and in response to apoptosis. Shedding is mediated by ADAM17 with implications for platelet lifespan and TPO production. (C) GPV is susceptible to shedding by both ADAM10 and ADAM17 under conditions of collagen binding and platelet activation. ©, calmodulin.