Two mechanisms coordinate the recruitment of the chromosomal passenger complex to the plane of cell division

Mol Biol Cell. 2017 Dec 1;28(25):3634-3646. doi: 10.1091/mbc.E17-06-0399. Epub 2017 Sep 27.

Abstract

During cytokinesis, the chromosomal passenger complex (CPC) promotes midzone organization, specifies the cleavage plane, and regulates furrow contractility. The localizations of the CPC are coupled to its cytokinetic functions. At the metaphase-to-anaphase transition, the CPC dissociates from centromeres and localizes to midzone microtubules and the equatorial cortex. CPC relocalization to the cell middle is thought to depend on MKlp2-driven, plus end-directed transport. In support of this idea, MKlp2 depletion impairs cytokinesis; however, cytokinesis failure stems from furrow regression rather than failed initiation of furrowing. This suggests that an alternative mechanism(s) may concentrate the CPC at the division plane. We show here that direct actin binding, via the inner centromere protein (INCENP), enhances CPC enrichment at the equatorial cortex, thus acting in tandem with MKlp2. INCENP overexpression rescues furrowing in MKlp2-depleted cells in an INCENP-actin binding-dependent manner. Using live-cell imaging, we also find that MKlp2-dependent targeting of the CPC is biphasic. MKlp2 targets the CPC to the anti-parallel microtubule overlap of the midzone, after which the MKlp2-CPC complex moves in a nondirected manner. Collectively, our work suggests that both actin binding and MKlp2-dependent midzone targeting cooperate to precisely position the CPC during mitotic exit, and that these pathways converge to ensure successful cleavage furrow ingression.

MeSH terms

  • Anaphase / physiology
  • Aurora Kinase B / metabolism
  • Cell Division / genetics
  • Cell Division / physiology*
  • Centromere / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomal Proteins, Non-Histone / physiology*
  • Chromosome Segregation / physiology*
  • Chromosomes / metabolism
  • Cytokinesis / physiology
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Kinesin / metabolism
  • Kinesin / physiology
  • Metaphase / physiology
  • Microfilament Proteins / metabolism
  • Microtubules / metabolism
  • Spindle Apparatus / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • INCENP protein, human
  • KIF20A protein, human
  • Microfilament Proteins
  • Aurora Kinase B
  • Kinesin