title: Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes.
abstract: Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK m.platani@ed.ac.uk Bill.Earnshaw@ed.ac.uk.
authors.forename: Melpomeni
authors.initials: M
authors.lastname: Platani
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H8M5, Canada Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario K1H8M5, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Trinkle-Mulcahy
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Porter
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK.
authors.forename: A Arockia
authors.initials: AA
authors.lastname: Jeyaprakash
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK m.platani@ed.ac.uk Bill.Earnshaw@ed.ac.uk.
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
mesh_terms: D000595:Amino Acid Sequence; D064096:Aurora Kinase A / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000201:enzymology*; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064096:Aurora Kinase A; D018797:Cell Cycle Proteins; D016547:Kinesins; D009363:Neoplasm Proteins; D028861:Nuclear Pore Complex Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D058570:TOR Serine-Threonine Kinases; D000097869:Polo-Like Kinase 1; C465041:DLGAP5 protein, human; C091489:KIF2C protein, human; C512772:NUP107 protein, human; C546842:MTOR protein, human; C576917:AURKA protein, human