Modulation of gurken translation by insulin and TOR signaling in Drosophila.
Localized Gurken (Grk) translation specifies the anterior-posterior and dorsal-ventral axes of the developing Drosophila oocyte; spindle-class females lay ventralized eggs resulting from inefficient grk translation. This phenotype is thought to result from inhibition of the Vasa RNA helicase. In a screen for modifiers of the eggshell phenotype in spn-B flies, we identified a mutation in the lnk gene. We show that lnk mutations restore Grk expression but do not suppress the persistence of double-strand breaks nor other spn-B phenotypes. This suppression does not affect Egfr directly, but rather overcomes the translational block of grk messages seen in spindle mutants. Lnk was recently identified as a component of the insulin/insulin-like growth factor signaling (IIS) and TOR pathway. Interestingly, direct inhibition of TOR with rapamycin in spn-B or vas mutant mothers can also suppress the ventralized eggshell phenotype. When dietary protein is inadequate, reduced IIS-TOR activity inhibits cap-dependent translation by promoting the activity of the translation inhibitor eIF4E-binding protein (4EBP). We hypothesize that reduced TOR activity promotes grk translation independent of the canonical Vasa- and cap-dependent mechanism. This model might explain how flies can maintain the translation of developmentally important transcripts during periods of nutrient limitation when bulk cap-dependent translation is repressed.
Department of Biology SUNY Fredonia, Fredonia, NY 14063, USA. scott.ferguson@fredonia.edu
Scott B
SB
Ferguson
Malachi A
MA
Blundon
Martha S
MS
Klovstad
Trudi
T
Schüpbach
D000818:Animals; D030801:Animals, Genetically Modified; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005260:Female; D007328:Insulin / Q000502:physiology*; D008297:Male; D014176:Protein Biosynthesis / Q000502:physiology; D012315:RNA Caps / Q000502:physiology; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D007328:Insulin; D012315:RNA Caps; D016211:Transforming Growth Factor alpha; C083730:grk protein, Drosophila; D058570:TOR Serine-Threonine Kinases; D020365:RNA Helicases