Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes.
Bottom Line: 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.
Affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK email@example.com Bill.Earnshaw@ed.ac.uk.Show MeSH
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Mentions: To allow a quantitative measurement of spindle assembly and chromosome alignment, we examined the recovery of Mio-depleted cells from Monastrol, a kinesin Eg5 inhibitor that arrests mitotic cells in prometaphase with monopolar spindles without affecting microtubule dynamics (Kapoor et al., 2000). At 30 min after Monastrol washout, control mitotic cells had rapidly formed a bipolar spindle, with only 40% of cells still having a disorganized spindle. In contrast, at 30 min after Monastrol washout, Mio-depleted cells had a pronounced delay in bipolar spindle formation, with 76% of cells having monopolar or incomplete bipolar spindles (Fig. 4).
Affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK firstname.lastname@example.org Bill.Earnshaw@ed.ac.uk.