Membrane Deformation and Lipid Signaling: Functions of srGAP Family Proteins and PI(4,5)P2 Public Deposited

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  • March 22, 2019
Creator
  • Coutinho-Budd, Jaeda
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • The plasma membrane plays a structural and functional role in the life of a cell. Not only does it aid in encapsulating the intracellular contents to separate one cell from the next, but it also serves as an achor for the actin cytoskeleton scaffold, as well as a home base for lipids that serve as messengers in a number of downstream signaling pathways. Given the importance of these aspects in cellular regulation, variations in the plasma membrane could lead to vast consequences in cellular function. This work explores plasma membrane alterations in two ways: 1) investigating membrane deformation by the slit-robo GTPase Activating Protein (srGAP) proteins of the Bin/Amphiphysin/Rvs (BAR) superfamily, and 2) reducing the levels of phosphatidylinositol (4-5)-bisphosphate (PI(4,5)P2) using chemical dimerization. The work presented in this thesis demonstrates that srGAP2 can induce neurite outgrowth and branching, and inhibit migration of cortical pyramidal neurons, through the ability of its N-terminal F-BAR domain to induce filopodia-like protrusions. srGAP2 is more potent at inducing protrusions than srGAP1 or srGAP3 in non-neuronal cells, an activity mimicked by their respective F-BAR domains. This work also explores the ways in which the F-BARs of srGAP proteins vary in their regulation of membrane dynamics. Finally, this work investigates the feasibility of using rapamycin-inducible translocation of the yeast 5-phosphatase to deplete PI(4,5)P2 in vivo.
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  • In Copyright
Advisor
  • Polleux, Franck
Degree
  • Doctor of Philosophy
Graduation year
  • 2012
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