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The evolution of platelet responses to collagen under conditions of hemodynamic flow / Alec A. Schmaier.
LIBRA R001 2010 .S347
Available from offsite location
- Format:
- Book
- Manuscript
- Thesis/Dissertation
- Author/Creator:
- Schmaier, Alec A.
- Language:
- English
- Subjects (All):
- Penn dissertations--Pharmacological sciences.
- Pharmacological sciences--Penn dissertations.
- Pharmacological Sciences.
- Academic Dissertations as Topic.
- Medical Subjects:
- Pharmacological Sciences.
- Academic Dissertations as Topic.
- Local Subjects:
- Penn dissertations--Pharmacological sciences.
- Pharmacological sciences--Penn dissertations.
- Physical Description:
- xi, 165 pages : illustrations (some color) ; 29 cm
- Production:
- 2010.
- Summary:
- 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 alpha2bbeta3 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.
- Notes:
- Advisers: Mark L. Kahn; David E. Boettiger.
- Thesis (Ph.D. in Pharmacological Sciences) -- University of Pennsylvania, 2010.
- Includes bibliographical references.
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