LGN-Dependent Microtubule Regulation Influences Endothelial Cell Migration, Adhesion, and Sprout Integrity Public Deposited

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  • March 19, 2019
Creator
  • Wright, Catherine
    • Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
Abstract
  • Blood vessels form during organismal development and maintain integrity to provide oxygen and nutrients to the tissues. Vessels are comprised of endothelial cells that coordinate their individual behaviors to generate functional sprouts. Endothelial cells undergo directional migration, oriented divisions, and lumen formation through organization of the microtubule network. Microtubules are actively growing and shrinking polymers that direct the shape and movement of cells. Disruption of the microtubule network is detrimental for the cell. Here I investigated the role of the mitotic polarity protein LGN in endothelial cells and sprouting angiogenesis. To study LGN in the vasculature, I utilized a three-dimensional model for sprouting angiogenesis. Surprisingly, loss of LGN did not affect oriented division of endothelial cells within a sprout, but perturbed overall sprouting and branching. I utilized two-dimensional assays to investigate the cause behind three-dimensional sprout defects in LGN KD endothelial cells. At the cellular level, LGN KD resulted in reduced endothelial cell migration and dysregulated cell-cell adhesions. Endothelial cells with LGN knockdown displayed stabilized microtubules at the growing plus-end. The data fits a model in which LGN promotes turnover of microtubules in endothelial cells, which in turn regulates migration, cell-cell adhesion, and angiogenic sprouting.
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  • In Copyright
Advisor
  • Goldstein, Bob
  • Tzima, Eleni
  • Rogers, Stephen
  • Dudley, Andrew
  • Bautch, Victoria
  • Cook, Jean
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
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  • Chapel Hill, NC
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