Signaling mechanisms associated with the platelet collagen receptors
Marjoram, Robin James
Cellular adhesions to the extracellular matrix (ECM) and to neighboring cells are vital interactions within metazoans. This dissertation examines cellular adhesion by utilizing the adhesive interaction between platelets and collagens that occurs at vascular wound sites and is a crucial step in hemostasis. Platelets are central elements in maintaining an intact circulatory system, but they also have a significant role in thrombotic pathologies such as heart attack and stroke. I analyze the contributions that the two platelet surface receptors, á2â1 integrin (á2â1) and glycoprotein VI (GPVI)/Fc receptor ã-chain (FcRã) complex, make toward the platelet’s interaction with collagens at vascular wound sites as well as the cooperation of G protein-coupled receptor (GPCR) signaling in the adhesion process. We demonstrate a novel mechanism of modulating the avidity of á2â1 for collagens that causes an increase in platelet adhesion and that is triggered through GPCR and GPVI/FcRã activation of phospholipase C (PLC). A discussion is included on platelet adhesion and signaling involved in hemostasis and thrombosis, substrate/integrin interactions, and anti-platelet therapies.