title: Aurora kinases phosphorylate Lgl to induce mitotic spindle orientation in Drosophila epithelia.
abstract: The Lethal giant larvae (Lgl) protein was discovered in Drosophila as a tumor suppressor in both neural stem cells (neuroblasts) and epithelia. In neuroblasts, Lgl relocalizes to the cytoplasm at mitosis, an event attributed to phosphorylation by mitotically activated aPKC kinase and thought to promote asymmetric cell division. Here we show that Lgl also relocalizes to the cytoplasm at mitosis in epithelial cells, which divide symmetrically. The Aurora A and B kinases directly phosphorylate Lgl to promote its mitotic relocalization, whereas aPKC kinase activity is required only for polarization of Lgl. A form of Lgl that is a substrate for aPKC, but not Aurora kinases, can restore cell polarity in lgl mutants but reveals defects in mitotic spindle orientation in epithelia. We propose that removal of Lgl from the plasma membrane at mitosis allows Pins/LGN to bind Dlg and thus orient the spindle in the plane of the epithelium. Our findings suggest a revised model for Lgl regulation and function in both symmetric and asymmetric cell divisions.
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Bell
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Georgina C
authors.initials: GC
authors.lastname: Fletcher
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Brain
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: barry.thompson@cancer.org.uk.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Thompson
mesh_terms: D000818:Animals; D064127:Aurora Kinases / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D008938:Mitosis; D058953:Neural Stem Cells / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D008941:Spindle Apparatus / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014921:Wings, Animal / Q000254:growth & development
chemical_list: D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; D064127:Aurora Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C