Research

Biochemistry of Platelet Function

The prothrombinase complex, a membrane-bound, Ca2+-dependent complex comprised of the serine protease factor Xa and its essential cofactor factor Va, catalyzes the generation of thrombin and serves a critical role in hemostasis. While approximately 80% of the procofactor, factor V, is found in plasma, it is the remaining 20% found in the α-granules of platelets that constitutes the physiologically-relevant source of the molecule. The activation of platelets at sites of vascular injury results in release of the α-granule’s contents, providing a highly-concentrated bolus of the platelet-derived cofactor at a membrane surface where it can immediately support clot formation. As a member of Dr. Paula Tracy’s research group, I am interested in the role that platelets play in hemostasis, with a focus on understanding how the unique structural properties of platelet-derived factor Va make it such a robust cofactor for platelet-bound prothrombinase. To this end, a variety of physical and biochemical techniques are being used to characterize the unique post-translational modifications found on platelet-derived factor Va, so that these structural attributes of the cofactor may ultimately be related to the cofactor’s unique functional properties. Of similar interest are the origins of these unique modifications. Platelet-derived factor Va is formed within megakaryocytes, the progenitor cells of platelets, subsequent to the endocytosis of factor V from plasma. Such alteration and repackaging of an endocytosed molecule in preparation for subsequent use represents a novel paradigm in cellular trafficking, and identifying the locations and mechanisms involved in this process will provide new insights into the biological processes of cells. Ultimately, our detailed understanding of platelet-bound prothrombinase will enable increasingly well informed decisions to be made in the context of clinical interventions aimed at maintaining hemostasis and ameliorating its pathological extension, thrombosis.