Date of Award


Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)



First Advisor

Alexey Veraksa

Second Advisor

Linda Huang

Third Advisor

Kellee Harris-Siegfried


Arrestins are ubiquitous adaptor proteins that are implicated in diverse signaling pathways. Arrestins are involved in the regulation of G-protein coupled receptors (GPCRs) via endocytosis and desensitization followed by degradation or recycling of the receptor. There are two β-arrestin homologs in mammals, which are largely redundant and therefore difficult to study. Drosophila has a single β-arrestin, Kurtz (Krz), and hence presents unique opportunities to study the functions of β-arrestin. krz maternal mutants have been shown to cause defects in the gastrulation of Drosophila embryos. These were attributed to effects of Krz on Toll signaling pathway. To investigate the origins of the defects, the early hours of embryo development needed to be examined. One of the main pathways activated during the first hours of gastrulation that enables epithelial remodeling and ventral furrow formation is Fog-Mist signaling. Mist is a GPCR that is activated by Fog, which triggers a cascade of downstream signaling followed by phosphorylation of the regulatory light chain of myosin. Acto-myosin network of the cytoskeleton enables apical constriction of cells. Contracted cells exert mutual pull inward of the embryo forming the mesoderm, and the gap on the ventral side seals. Fog signaling is negatively regulated by G protein coupled receptor kinase 2 (GPRK2) that might be aiding desensitization of the receptor. gprk2 mutant embryos exhibit characteristic open defects of gastrulation, specifically wide opening in ventral furrow, suggesting over-activity of Fog signaling. In this study I investigate the role of Krz in Fog-Mist signaling and the effects of Krz on epithelial morphogenesis during Drosophila development. I present data that suggests Krz involvement in epithelial morphogenesis and perhaps negative regulation of Fog signaling via interaction with GPCR Mist. I have uncovered that embryos with decreased level of Krz show ventral furrow defects that lack closure similar to those of gprk2 mutants, moreover knockdown and overexpression Krz in wing discs causes changes in tissue fold formation where Fog signaling is also known to be active. A decrease in Krz levels causes a drop in the number of severe leg phenotypes in mist mutant flies. Data in cell culture suggest that Krz and Mist colocalize in cytoplasmic puncta upon Fog stimulation. Krz role in development is still not well understood, and studying its function in Fog-Mist signaling has a potential to uncover new importance of this protein as well as help to elucidate the mechanisms of downregulation in the Fog-Mist pathway.


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