Dissertations, Theses, and Capstone Projects

Date of Degree

6-2020

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor

Derrick T. Brazill

Committee Members

Patricia Rockwell

Peter Lipke

David Foster

Jeffrey E. Segall

Subject Categories

Cell Biology | Developmental Biology | Molecular Biology

Keywords

Dictyostelium discoideum, cell signaling, actin cytoskeleton, Protein Kinase C, Phospholipase D, p21-activated kinase

Abstract

Proper regulation of the actin cytoskeleton is crucial to many cellular processes. Many of these processes are regulated by extracellular signaling cues, which direct changes in the actin cytoskeleton, resulting in changes to cellular morphology, and directed motility. The social amoeba, Dictyostelium discoideum, is used as a simple model system to study the translation of extracellular signals to the actin cytoskeleton. When starved, these unicellular amoebae undergo a multicellular developmental process characterized by a tightly regulated sequence of signaling events. This results in chemotaxis and formation of a multicellular aggregate, and ultimately cell differentiation and the formation of a fruiting body. pkcA, a putative Protein Kinase C-orthologue, has previously been shown to regulate development and fruiting body formation. Here we show that pkcA is involved in cell density sensing, chemotactic signaling, cell morphology, and cell-cell cohesion. Additionally, we show through epistasis analysis, that pkcA regulates these processes through a functional interaction with pldB, a D. discoideum PLD-orthologue. Lastly, we provide evidence that pakD, a p21-activated kinase, acts between pkcA and pldB in the regulation of development. Given that both pldB and pakD have been shown to regulate the actin cytoskeleton during chemotaxis and development, this provides a mechanism for pkcA to influence the organization and assembly of the actin cytoskeleton.

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