Date of Award

8-1-2013

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Alexey Veraksa

Second Advisor

Gregory Beck

Third Advisor

Richard Kesseli

Abstract

β-arrestins are adaptor proteins involved in the regulation of many signaling pathways, including MAP Kinases and the transcription factor NF-κB. Previously our laboratory demonstrated that β-arrestin Kurtz (Krz), the only β-arrestin homolog in Drosophila melanogaster, negatively regulates the Toll signaling pathway in the embryo. This pathway also has a highly conserved function in innate immunity in many organisms, including humans and flies. Toll signaling pathway is activated as a result of grampositive infection. Activation of Toll signaling induces nuclear translocation of the NF-κB family proteins and expression of Toll target genes. Dorsal (Dl), a homolog of the mammalian NF-κB proteins, is primarily localized in the cytoplasm. However, Toll gainof-function or mutation in the Cactus, a homolog of the mammalian IκB, or the injury of the third instar larvae results in translocation of Dl to the nucleus. I present evidence that mutations in krz result in an abnormal upregulation of Toll signaling at the larval stages. I have also found that loss of krz function promotes apoptosis. Apoptosis is the ability of cells to destroy themselves when their death is beneficial to the organism. Hallmarks of apoptosis are the fragmentation of DNA and activation of initiator caspases. I observed the presence of fragmented DNA as well as activated initiator caspases in the krz mutant cells. In this study, I investigate the functional role of krz in apoptosis by examining the relationship between Toll pathway activation and apoptosis, as well as possible molecular mechanisms that lead to apoptosis in krz mutants.

Comments

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