Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis

Curr Biol. 2005 Apr 26;15(8):778-86. doi: 10.1016/j.cub.2005.03.041.

Abstract

The central spindle regulates the formation and positioning of the contractile ring and is essential for completion of cytokinesis [1]. Central spindle assembly begins in early anaphase with the bundling of overlapping, antiparallel, nonkinetochore microtubules [2, 3], and these bundles become compacted and mature into the midbody. Prominent components of the central spindle include aurora B kinase and centralspindlin, a complex containing a Kinesin-6 protein (ZEN-4/MKLP1) and a Rho family GAP (CYK-4/MgcRacGAP) that is essential for central spindle assembly [4]. Centralspindlin localization depends on aurora B kinase [5]. Aurora B concentrates in the midbody and persists between daughter cells. Here, we show that in C. elegans embryos and in cultured human cells, respectively, ZEN-4 and MKLP1 are phosphorylated by aurora B in vitro and in vivo on conserved C-terminal serine residues. In C. elegans embryos, a nonphosphorylatable mutant of ZEN-4 localizes properly but does not efficiently support completion of cytokinesis. In mammalian cells, an inhibitor of aurora kinase acutely attenuates phosphorylation of MKLP1. Inhibition of aurora B in late anaphase causes cytokinesis defects without disrupting the central spindle. These data indicate a conserved role for aurora-B-mediated phosphorylation of ZEN-4/MKLP1 in the completion of cytokinesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Blotting, Western
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / metabolism*
  • Cloning, Molecular
  • Cytokinesis / physiology*
  • Electrophoresis, Polyacrylamide Gel
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Kinesin / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / metabolism*
  • Transfection

Substances

  • Caenorhabditis elegans Proteins
  • MKLP1 protein, C elegans
  • Microtubule-Associated Proteins
  • ZEN-4 protein, C elegans
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Kinesin