title: Sgt1 acts via an LKB1/AMPK pathway to establish cortical polarity in larval neuroblasts.
abstract: Drosophila neuroblasts are a model system for studying stem cell self-renewal and the establishment of cortical polarity. Larval neuroblasts generate a large apical self-renewing neuroblast, and a small basal cell that differentiates. We performed a genetic screen to identify regulators of neuroblast self-renewal, and identified a mutation in sgt1 (suppressor-of-G2-allele-of-skp1) that had fewer neuroblasts. We found that sgt1 neuroblasts have two polarity phenotypes: failure to establish apical cortical polarity at prophase, and lack of cortical Scribble localization throughout the cell cycle. Apical cortical polarity was partially restored at metaphase by a microtubule-induced cortical polarity pathway. Double mutants lacking Sgt1 and Pins (a microtubule-induced polarity pathway component) resulted in neuroblasts without detectable cortical polarity and formation of "neuroblast tumors." Mutants in hsp83 (encoding the predicted Sgt1-binding protein Hsp90), LKB1, or AMPKα all show similar prophase apical cortical polarity defects (but no Scribble phenotype), and activated AMPKα rescued the sgt1 mutant phenotype. We propose that an Sgt1/Hsp90-LKB1-AMPK pathway acts redundantly with a microtubule-induced polarity pathway to generate neuroblast cortical polarity, and the absence of neuroblast cortical polarity can produce neuroblast tumors.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Andersen
authors.forename: Doug W
authors.initials: DW
authors.lastname: Turnbull
authors.forename: Eric A
authors.initials: EA
authors.lastname: Johnson
authors.forename: Chris Q
authors.initials: CQ
authors.lastname: Doe
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins; D016764:Cell Polarity / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003703:Demecolcine / Q000494:pharmacology; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D006360:Heat-Shock Proteins; C089272:Hsp83 protein, Drosophila; D018832:Molecular Chaperones; C405164:Pins protein, Drosophila; C538796:Sgt1 protein, Drosophila; D050257:Tubulin Modulators; D011494:Protein Kinases; C523914:AMPKalpha protein, Drosophila; C495775:LKB1 protein, Drosophila; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D003703:Demecolcine