Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A

J Cell Biol. 2019 Feb 3;219(2):e201905194. doi: 10.1083/jcb.201905194.

Abstract

Aurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase, thereby locally regulating factors that promote spindle organization, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1 or are deficient for Aurora kinase regulation. By analyzing these mutants, we show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Anaphase / physiology
  • Aurora Kinase A / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Chromosome Positioning / physiology
  • Chromosome Segregation / physiology*
  • Chromosomes / metabolism*
  • Chromosomes / physiology*
  • DNA-Binding Proteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kinesins / metabolism*
  • Microtubules / metabolism
  • Mitosis / physiology
  • Multiprotein Complexes / metabolism*
  • Phosphorylation / physiology
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology

Substances

  • DNA-Binding Proteins
  • Multiprotein Complexes
  • condensin complexes
  • AURKA protein, human
  • Aurora Kinase A
  • Adenosine Triphosphatases
  • KIF4A protein, human
  • Kinesins