Date of Award
Summer 2010
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
First Advisor
Mark L. Kahn
Abstract
Collagen activates platelets through the immune-type GPVI receptor, but the mechanism by which this receptor has adapted to function in platelets under conditions of rapid blood flow is unclear. Additionally, it is unknown if responses to collagen are conserved in nucleated thrombocytes found in non-mammalian vertebrates, which do not express GPVI. Here we show that the GPVI proline-rich domain accelerates GPVI signaling kinetics and is required for maximal adhesion to collagen under flow. The proline-rich domain accelerates signaling through binding and directly activating the Src-family kinase Lyn. Chicken thrombocytes are potently activated by collagen but do not form 3-dimensional aggregates under arterial flow conditions, a profound contrast to platelet function. Despite selective expression of most platelet-specific genes, thrombocytes contain a significantly lower density of α2bβ3 integrin on the cell surface. These studies identify a novel molecular mechanism by which GPVI accelerates immune signaling kinetics and demonstrate partial conservation of hemostatic cell responses to collagen under flow.
Recommended Citation
Schmaier, Alec A., "The Evolution of Platelet Responses to Collagen Under Conditions of Hemodynamic Flow" (2010). Publicly Accessible Penn Dissertations. 203.
https://repository.upenn.edu/edissertations/203
Additional Files
Supplemental movie 3-1.mov (42078 kB)Supplemental Movie 3-1
Supplemental movie 3-2.mov (46288 kB)
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Supplemental Movie 3-6
Included in
Biochemistry Commons, Cardiology Commons, Cellular and Molecular Physiology Commons, Comparative and Evolutionary Physiology Commons, Other Immunology and Infectious Disease Commons, Poultry or Avian Science Commons