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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aurora Kinase A / physiology*
  • Cell Cycle Proteins / metabolism*
  • Centrosome / enzymology*
  • Enzyme Activation
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Kinesin / metabolism
  • Mitosis
  • Molecular Sequence Data
  • Neoplasm Proteins / metabolism
  • Nuclear Pore Complex Proteins / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Spindle Apparatus / metabolism
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Cell Cycle Proteins
  • DLGAP5 protein, human
  • KIF2C protein, human
  • NUP107 protein, human
  • Neoplasm Proteins
  • Nuclear Pore Complex Proteins
  • Proto-Oncogene Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AURKA protein, human
  • Aurora Kinase A
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Kinesin

Associated data

  • PDB/4ORH