A GENETIC MODIFIER SCREEN IDENTIFIES MULTIPLE GENES THAT INTERACT WITH DROSOPHILA RAP FZR AND SUGGESTS NOVEL CELLULAR ROLES

• Published in: Journal of neurogenetics Vol. 21; no. 3; pp. 105 - 151
• Main Authors: Kaplow, Margarita E., Mannava, Laura J., Pimentel, Angel C., Fermin, Hector A., Hyatt, Vanetta J., Lee, John J., Venkatesh, Tadmiri R.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.07.2007; Taylor & Francis
• Subjects: Anaphase promoting complex; Animals; Cell-cycle; Cyclin-Dependent Kinases - genetics; Cyclins - genetics; Drosophila - embryology; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; E3-ligase; Eye - embryology; Eye - ultrastructure; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genes, Insect; Genetic enhancers; Genetic suppressors; Larva; Male; Microscopy, Electron, Scanning; Mitotic exit; Oligonucleotide Array Sequence Analysis; Retina patterning; Transposon mutagenesis; Ubiquitin-Protein Ligases - genetics; Ubiquitination
• ISSN: 0167-7063; 1563-5260
• DOI: 10.1080/01677060701503140

In the developing Drosophila eye, Rap Fzr plays a critical role in neural patterning by regulating the timely exit of precursor cells. Rap Fzr (Retina aberrant in pattern Fizzy related) is an activator of the E3 Ubiquitin ligase, the APC (Anaphase Promoting Complex-cyclosome) that facilitates the stage specific proteolytic destruction of mitotic regulators, such as cyclins and cyclin-dependent kinases. To identify novel functional roles of Rap Fzr, we conducted an F1 genetic modifier screen to identify genes which interact with the partial-loss-function mutations in rap fzr. We screened 2741 single P-element, lethal insertion lines and piggyBac lines on the second and third chromosome for dominant enhancers and suppressors of the rough eye phenotype of rap fzr. From this screen, we have identified 40 genes that exhibit dosage-sensitive interactions with rap fzr; of these, 31 have previously characterized cellular functions. Seven of the modifiers identified in this study are regulators of cell cycle progression with previously known interactions with rap fzr. Among the remaining modifiers, 27 encode proteins involved in other cellular functions not directly related to cell-cycle progression. The newly identified variants fall into at least three groups based on their previously known cellular functions: transcriptional regulation, regulated proteolysis, and signal transduction. These results suggest that, in addition to cell cycle regulation, rap fzr regulates ubiquitin-ligase-mediated protein degradation in the developing nervous system as well as in other tissues.