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 firstname.lastname@example.org Bill.Earnshaw@ed.ac.uk.Show MeSH
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Mentions: Seh1 is a member of the Nup107 complex that functions in NPC assembly and localizes to kinetochores in mitosis (Belgareh et al., 2001). To better define its biochemical interactions in mammalian cells, we isolated GFP-Seh1 both from asynchronous and mitotically arrested HeLaGFPSeh1 cells (Platani et al., 2009) and identified interacting proteins by SILAC (stable isotope labeling by amino acids in cell culture) mass spectrometry (Ong and Mann, 2007). This analysis identified all known Seh1-interacting proteins, including components of the Nup107 complex (Nup107, 98, 133, 160, and 85) and SEACAT/GATOR2 complexes (Mios, WDR24, and WDR59; Fig. 1 A and Fig. S1 A; Dokudovskaya et al., 2011; Bar-Peled et al., 2013; Panchaud et al., 2013a). Interestingly, Seh1 interacts with the SEACAT/GATOR2 complex equally in interphase and mitosis, whereas its interaction with the rest of the Nup107 complex is stronger during mitosis.
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.