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Title page for ETD etd-02182011-143449


Type of Document Dissertation
Author Marjoram, Robin James
Author's Email Address robin.j.marjoram@vanderbilt.edu
URN etd-02182011-143449
Title Signaling mechanisms associated with the platelet collagen receptors
Degree PhD
Department Pathology
Advisory Committee
Advisor Name Title
Mary Zutter Committee Chair
Andries Zijlstra Committee Member
Billy Hudson Committee Member
David Friedman Committee Member
Jay Jerome Committee Member
Samuel Santoro Committee Member
Keywords
  • cell biology
  • biochemistry
  • pathology
Date of Defense 2011-01-20
Availability unrestricted
Abstract
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.
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