Description
- Abstract:
- Cell division is fundamental to life. As more divergent organisms become tractable to genetic manipulation, we have discovered that the molecular mechanisms that govern cell division are as variable as the organisms themselves. The unicellular protist parasite Trypanosoma brucei, the causative agent of African sleeping sickness, is separated from humans by 1 billion years of evolution. It has a highly asymmetric cell shape with a broad posterior and narrow anterior that is created by an extensive cytoskeletal structure known as the subpellicular array. The subpellicular array consists of a single layer of crosslinked microtubules that underlie the plasma membrane and persist throughout the cell cycle. To divide, T. brucei has developed a unique mode of cytokinesis that maintains cell shape and ensures array integrity. It does not employ an actomyosin contractile ring as in yeast and metazoan systems; rather, cytokinesis takes place asymmetrically along the long axis of the cell. Cleavage furrow ingression initiates at the narrow cell anterior and follows the helical path of array microtubules towards the cell posterior. However, the molecular mechanisms that govern this unique mode of cytokinesis while maintaining array shape are not known. In this dissertation, we explore the link between cytokinesis and cell shape in T. brucei. In Chapter 2, we determine that the first cytokinetic protein discovered in T. brucei, TOEFAZ1, functions as a scaffold to recruit cytokinetic regulators to the initiation point of cleavage furrow ingression. This work precipitated multiple protein-proximity interaction assays to identify TOEFAZ1 binding partners that are involved subpellicular array remodeling during cytokinesis, which led to the discovery of PAVE1. In Chapter 3, we find that PAVE1 is a component of the inter-microtubule crosslinks of the subpellicular array and is necessary to maintain the length and shape of the array at the cell posterior. We also discover that the array is organized into subdomains characterized by the differential localization of array-associated proteins that locally tune array shape. The work presented in this thesis establishes the foundation for understanding the molecular mechanism of cytokinesis in T. brucei, which is inseparable from the cellular architecture created by the subpellicular array.
- Notes:
- Thesis (Ph. D.)--Brown University, 2021
Citation
Sinclair Roth, Amy,
"Cytoskeletal morphogenesis in Trypanosoma brucei"
(2021).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:26rh3kru/
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....