title: Model systems for platelet receptor shedding.
abstract: Platelet adhesion and aggregation at sites of vascular injury are crucial for hemostasis; however, under pathological conditions, they can cause myocardial infarction and stroke. Platelet adhesion is mediated by binding of the glycoprotein (GP)Ib-V-IX complex to immobilized von Willebrand factor (vWF), thereby enabling the interaction of GPVI with exposed collagen and subsequent platelet activation. This process is reinforced by locally produced thrombin and platelet-derived adenosine diphosphate (ADP) and thromboxane A2 (TxA2), leading to a conformational change of integrins from a low- to a high-affinity state, which allows firm platelet adhesion and aggregation. Stable platelet aggregation requires the formation of fibrin and the coordinated interaction of additional receptors on the adjacent platelets. Platelet surface receptor expression can partially be regulated by proteolytic cleavage, which may represent a mechanism to downregulate platelet reactivity toward extracellular matrix proteins and ligands. It is estimated that approximately 10% of platelet surface receptors are regulated by proteolytic cleavage. In this chapter of the review series we will summarize the platelet receptors that are known to be shed from the cell surface with a focus on the proteins GPIbα, GPV and GPVI, which are cleaved by members of the 'a disintegrin and metalloproteinase' (ADAM) family.
authors.affiliation: a Department of Experimental Biomedicine , University of Würzburg, University Hospital and Rudolf Virchow Center , Würzburg , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bender
authors.affiliation: a Department of Experimental Biomedicine , University of Würzburg, University Hospital and Rudolf Virchow Center , Würzburg , Germany.
authors.forename: David
authors.initials: D
authors.lastname: Stegner
authors.affiliation: a Department of Experimental Biomedicine , University of Würzburg, University Hospital and Rudolf Virchow Center , Würzburg , Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015539:Platelet Activation; D010973:Platelet Adhesiveness
keywords: GPIb; GPV; GPVI; metalloproteinase; platelet; receptor shedding