Regulation of platelet membrane protein shedding in health and disease

Extracellular proteolysis of platelet plasma membrane proteins is an event that ensues platelet activation. Shedding of surface receptors such as glycoprotein (GP) Ibα, GPV and GPVI as well as externalized proteins P-selectin and CD40L releases soluble ectodomain fragments that are subsequently detectable in plasma. This results in the irreversible functional downregulation of platelet receptor-mediated adhesive interactions and the generation of biologically active fragments. In this review, we describe molecular insights into the regulation of platelet receptor and ligand shedding in health and disease. The scope of this review is specially focused on GPIbα, GPV, GPVI, P-selectin and CD40L where we: (1) describe the basic physiological regulation of expression and shedding of these proteins in hemostasis illustrate alterations in receptor expression during (2) apoptosis and (3) ex vivo storage relevant for blood banking purposes; (4) discuss considerations to be made when analyzing and interpreting shedding of platelet membrane proteins and finally; (5) collate clinical evidence that quantify these platelet proteins during disease.