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Regulation of Septum Formation by Two Novel Proteins Art1 and Bga1 in Fission Yeast Cytokinesis

Davidson, Reshma

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Molecular, Cellular and Developmental Biology.
Cytokinesis is the final step in the cell cycle that partitions a mother cell into two daughter cells. The final step in cytokinesis involves extracellular matrix formation/ remodelling and midbody abscission in mammals. Many of the proteins and steps involved in cytokinesis are conserved from yeast to mammals. This makes genetically tractable unicellular fission yeast a good model system to study cytokinesis. In fission yeast extracellular matrix remodeling involves the deposition of a trilaminar polysaccharide septum and its subsequent digestion to separate the two daughter cells. For my thesis I worked on two novel proteins that are involved in cytokinesis and the regulation of septum synthesis. The septum and the outer cell wall in fission yeast are rigid structures that protect the cell from environmental stresses and give the cell its characteristic rod shape. The process of cell wall and septum formation are tightly regulated. Rho GTPases, activated by guanine nucleotide exchange factors (GEFs), are essential regulators of polarized cell growth, cytokinesis, and many other cellular processes. Amongst other things, they control the function of the cell wall synthesizing enzymes. However, the regulations of Rho GEFs themselves are not well understood. For my first project I studied the regulation of the Rho GEF Rgf3. Rgf3 is an essential GEF for Rho1 GTPase in fission yeast. The regulation of Rho GEF is a well-studied topic although much remains to be understood regarding its different modes of regulation. I have shown a novel mechanism of regulation of Rgf3 protein level and localization by an arrestin-related protein Art1. I found that art1¿ cells have a defective septum similar to rgf3 mutants. Art1 binds Rgf3 and plays a role in maintaining Rgf3 cellular levels. Finally, in art1¿ cells the amount of active Rho GTPase found at the division site was also reduced. This showed that Art1 played a role in septum formation by regulating the levels of active Rho1 found at the division site, through regulation of Rgf3. For my second project I explored how the localization and level of the cell wall synthesizing enzyme are controlled. Regulation of fungal cell wall synthesis is of great interest due to the diseases and economic damage caused by several pathogenic fungi. ß-Glucan synthase 1 (Bgs1), popular anti-fungal drug target, synthesizes the linear 1,3-ß-glucan which is the main component of primary septum. Rho1 GTPase and the F-BAR protein Cdc15 are known to play a role in Bgs1 regulation. However, they also regulate the function of several other proteins during cytokinesis. No specific regulator for Bgs1 function was known. In my second project I have characterized a novel protein Bga1 that regulates Bgs1 protein levels and localization to the plasma membrane. Bga1 is essential for contractile-ring constriction and septum formation during cytokinesis. Bga1 and Bgs1 physically interact and are interdependent for localization to the plasma membrane. Furthermore, Bga1 plays an earlier and more important role in Bgs1 trafficking/localization than Cdc15.
Jian-Qiu Wu, PhD (Advisor)
163 p.

Recommended Citations

Citations

  • Davidson, R. (2016). Regulation of Septum Formation by Two Novel Proteins Art1 and Bga1 in Fission Yeast Cytokinesis [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1469185292

    APA Style (7th edition)

  • Davidson, Reshma. Regulation of Septum Formation by Two Novel Proteins Art1 and Bga1 in Fission Yeast Cytokinesis. 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1469185292.

    MLA Style (8th edition)

  • Davidson, Reshma. "Regulation of Septum Formation by Two Novel Proteins Art1 and Bga1 in Fission Yeast Cytokinesis." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1469185292

    Chicago Manual of Style (17th edition)