Characterization of atrogin in Drosophila melanogaster

Connors, Colleen B. (2012) Characterization of atrogin in Drosophila melanogaster. Masters thesis, Memorial University of Newfoundland.

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Abstract

The atrogin F-box protein plays a role in muscle wasting in many diseases including cancer, sepsis, AIDS, renal failure, COPD and more. In mammals, atrogin is a component of an E3 ligase that serves to add ubiquitin moieties to, or ubiquitinate, substrates. Some targets of atrogin, such as proteins essential for muscle synthesis, are ubiquitnated and tagged for degradation. However, other targets, such as foxo, that are ubiquitinated have enhanced activity. Although widely studied in vertebrate species, atrogin has yet to be characterized in Drosophila melanogaster. In this study, the D. melanogaster homologue of atrogin has been identified and characterized. The atrogin homologue in Drosophila has been partially conserved through evolution, and retains all of the functional domains. When overexpressed, atrogin can show a slight decrease in locomotor ability, longevity, ommatidia number and bristle number. When examining potential interactions between atrogin and foxo, it was shown that the overexpression of atrogin during nutritional stress enhances survivorship. Additionally, the co-expression of atrogin and foxo enhances the foxo phenotype as seen by a decrease in ommatidia number and increase of survivorship during nutritional stress. Finally, it was shown that atrogin suppresses the deleterious effect that PI31, a binding partner of FBXO7, has on the ommatidial array of the compound eye.

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