Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension

Dev Cell. 2012 May 15;22(5):1017-29. doi: 10.1016/j.devcel.2012.02.013.

Abstract

Alignment of chromosomes at the metaphase plate is a signature of cell division in metazoan cells, yet the mechanisms controlling this process remain ambiguous. Here we use a combination of quantitative live-cell imaging and reconstituted dynamic microtubule assays to investigate the molecular control of mitotic centromere movements. We establish that Kif18A (kinesin-8) attenuates centromere movement by directly promoting microtubule pausing in a concentration-dependent manner. This activity provides the dominant mechanism for restricting centromere movement to the spindle midzone. Furthermore, polar ejection forces spatially confine chromosomes via position-dependent regulation of kinetochore tension and centromere switch rates. We demonstrate that polar ejection forces are antagonistically modulated by chromokinesins. These pushing forces depend on Kid (kinesin-10) activity and are antagonized by Kif4A (kinesin-4), which functions to directly suppress microtubule growth. These data support a model in which Kif18A and polar ejection forces synergistically promote centromere alignment via spatial control of kinetochore-microtubule dynamics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosome Positioning / physiology*
  • Chromosomes, Human / metabolism*
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Kinesin / metabolism*
  • Kinetochores / metabolism*
  • Microtubules / metabolism*
  • Mitosis / physiology
  • Models, Biological
  • Spindle Apparatus / metabolism

Substances

  • KIF18A protein, human
  • KIF4A protein, human
  • Kinesin