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Sidney V Jones CHM MS Thesis 2014.pdf (2.96 MB)

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Effects of Shear Stress on the Distribution of Kindlins in Endothelial Cells

Jones, Sidney V
http://rave.ohiolink.edu/etdc/view?acc_num=csu1401283504

Abstract Details

2014, Master of Science in Chemistry, Cleveland State University, College of Sciences and Health Professions.
Endothelial cells (ECs) are exposed to changes in shear stress under a variety of physiological and pathological circumstances and respond by changing their shape, gene expression and cytoskeletal arrangement. Integrins are central mediators of these mechanotransduction responses of ECs and integrin function is in turn controlled by interaction of their short cytoplasmic tails with cytoplasmic binding partners. Recent studies have demonstrated the importance of the kindlin family members, known cytoplasmic tail binding proteins, as regulators of integrin function. Our lab has previously shown that kindlin-2 (K2) and kindlin-3 (K3) are both expressed and functionally significant for integrin mediated cellular events in ECs. The conversion of shear stress that realigns ECs in the direction of flow differentially affects the distribution of K2 and K3. This observation was made under shear stress rates of 3 or 10 dynes/cm2 in cells adherent to fibronectin. K2 is present in focal adhesion (FA) under static conditions and becomes redistributed into an increase number of FAs with decreased area and length in response to low shear stress. The change in distribution of K2 in response to flow may explain why its colocalization with VE-cadherin was increased in response to flow in a rate dependent manner. K3 changes from its primary and uniform cytosolic distribution to coalesce into discrete punctate patterns. The K3 punctate patterns were assessed for colocalization with clathrin coated vesicles and microtubules, which was significantly increased and decreased, respectively, under low flow. Shear stress induced kindlin-3 punctae formation corresponds to cleavage likely due to shear stress induced calpain activation. Inhibition of calpain prevents the effects of shear stress induced changes in K3 distribution. On ECs adherent to another matrix protein, laminin, kindlin-3 was observed to redistribute into focal adhesions in response to high flow, which is not fully understood. This report confirms that kindlin-2 and kindlin-3 respond differently to shear stress in ECs and that the shear stress induced protein redistribution is dependent on the magnitude and duration of flow. It also demonstrates how the intensity of flow and extracellular matrix substratum of the EC may be important regulators of the fate of intracellular proteins involved in mechanotransduction. Consequently, this study provides insight into spatiotemporal effects of flow on endothelial cells and suggests that kindlins participate in the adaptation of ECs to mechanical cues.
Edward F. Plow, PhD (Advisor)
Michael Kalafatis, PhD (Committee Chair)
David J. Anderson, PhD (Committee Member)
Crystal Weyman, PhD (Committee Member)
83 p.
Biochemistry; Biomechanics; Cellular Biology; Chemistry
integrin; kindlin; fibronectin; laminin; extracellular matrix; zyxin; tubulin; actin; clathrin; cytoskeletal rearrangment; hemodynamic; shear stress; endothelial cell; mechanotransduction; vinculin; cell-cell junction; atherosclerosis; colocalization

Recommended Citations

Citations

  • Jones, S. V. (2014). Effects of Shear Stress on the Distribution of Kindlins in Endothelial Cells [Master's thesis, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1401283504

    APA Style (7th edition)

  • Jones, Sidney. Effects of Shear Stress on the Distribution of Kindlins in Endothelial Cells. 2014. Cleveland State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1401283504.

    MLA Style (8th edition)

  • Jones, Sidney. "Effects of Shear Stress on the Distribution of Kindlins in Endothelial Cells." Master's thesis, Cleveland State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1401283504

    Chicago Manual of Style (17th edition)

csu1401283504
610
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This open access ETD is published by Cleveland State University and OhioLINK.