TOG Proteins: Essential +TIPs Regulators of Interphase Microtubule Dynamics Public Deposited

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Last Modified
  • March 22, 2019
Creator
  • Currie, Joshua David
    • Affiliation: College of Arts and Sciences, Department of Biology
Abstract
  • Microtubules exhibit a signature behavior, termed dynamic instability, in which individual microtubules cycle between phases of growth and shrinkage while the total microtubule polymer remains constant. These dynamics are promoted by the conserved XMAP215/Dis1 family of microtubule-associated proteins (MAPs). During my thesis I have conducted an in vivo structure-function analysis of the Drosophila homologue, Mini spindles (Msps). Msps exhibits EB1-dependent and spatially regulated localization to microtubules, localizing to microtubule plus ends in the cell interior and decorating the lattice of growing and shrinking microtubules in the cell periphery. RNAi rescue experiments revealed that Msps' NH2-terminal four TOG domains were sufficient to partially restore microtubule dynamics and promote EB1 comet formation and that TOG domains function as paired units. We also identified TOG5 and novel inter-TOG linker motifs that are sufficient for binding to the microtubule lattice. These novel microtubule contact sites are necessary for Msps peripheral lattice association and allow Msps to regulate dynamic instability. Additionally, I have been able to determine the region of Msps that is responsible for plus end tracking in cells. This occurs through a novel interaction with the EB1-binding protein, Sentin, that enhances Msps accumulation at the plus end and affects the velocity and lifetime of plus end growth. From these results we have learned that Msps is an important microtubule regulator that controls multiple parts of dynamic instability through its unique domain structure.
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  • In Copyright
Advisor
  • Rogers, Stephen
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2011
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