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J Cell Biol. 2015 Jul 6;210(1):45-62. doi: 10.1083/jcb.201410001. Epub 2015 Jun 29.

Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes.

Author information

1
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.
2
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.
3
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
4
Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK.

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.

PMID:
26124292
PMCID:
PMC4494011
DOI:
10.1083/jcb.201410001
[Indexed for MEDLINE]
Free PMC Article

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