Oskar is targeted for degradation by the sequential action of Par-1, GSK-3, and the SCF⁻Slimb ubiquitin ligase.
Translation of oskar messenger RNA (mRNA) is activated at the posterior of the Drosophila oocyte, producing Long Oskar, which anchors the RNA, and Short Oskar, which nucleates the pole plasm, containing the posterior and germline determinants. Here, we show that Oskar is phosphorylated by Par-1 and GSK-3/Shaggy to create a phosphodegron that recruits the SCF(-Slimb) ubiquitin ligase, which targets Short Oskar for degradation. Phosphorylation site mutations cause Oskar overaccumulation, leading to an increase in pole cell number and embryonic patterning defects. Furthermore, the nonphosphorylatable mutant produces bicaudal embryos when oskar mRNA is mislocalized. Thus, the Par-1/GSK-3/Slimb pathway plays important roles in limiting the amount of pole plasm posteriorly and in degrading any mislocalized Oskar that results from leaky translational repression. These results reveal that Par-1 controls the timing of pole plasm assembly by promoting the localization of oskar mRNA but inhibiting the accumulation of Short Oskar protein.
The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Eurico
E
Morais-de-Sá
Antonio
A
Vega-Rioja
Vítor
V
Trovisco
Daniel
D
St Johnston
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009866:Oogenesis / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; C091675:osk protein, Drosophila; C110233:slmb protein, Drosophila; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; C080335:Sgg protein, Drosophila; D038362:Glycogen Synthase Kinase 3; C472496:Par-1 protein, Drosophila