A genetic modifier screen identifies multiple genes that interact with Drosophila Rap/Fzr and suggests novel cellular roles.
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 F(1) 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.
Kaplow
Margarita E
ME
Department of Biology, City College and The Graduate Center, City University of New York, New York, NY 10031, USA.
Mannava
Laura J
LJ
Pimentel
Angel C
AC
Fermin
Hector A
HA
Hyatt
Vanetta J
VJ
Lee
John J
JJ
Venkatesh
Tadmiri R
TR
D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000196:embryology* / Q000648:ultrastructure; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D007814:Larva; D008297:Male; D008855:Microscopy, Electron, Scanning; D020411:Oligonucleotide Array Sequence Analysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
D016213:Cyclins; D029721:Drosophila Proteins; D044767:Ubiquitin-Protein Ligases; D018844:Cyclin-Dependent Kinases