Dual detection of chromosomes and microtubules by the chromosomal passenger complex drives spindle assembly

Dev Cell. 2010 Jun 15;18(6):903-12. doi: 10.1016/j.devcel.2010.05.018.

Abstract

Chromosome-dependent spindle assembly requires the chromosomal recruitment and activation of Aurora B, the kinase subunit of the chromosomal passenger complex (CPC). It remains unclear how the chromosome-activated kinase spatially transmits signals to organize the micron-scale spindle. Here we reveal that the CPC must detect two structures, chromosomes and microtubules, to support spindle assembly in Xenopus egg extracts. While Aurora B is enriched on chromosomes in metaphase, we establish that a fraction of Aurora B is targeted to the metaphase spindle and phosphorylates microtubule-bound substrates. We demonstrate that chromosomally activated Aurora B must be targeted to microtubules to drive spindle assembly. Moreover, although the CPC-microtubule interaction can activate Aurora B, which further promotes microtubule assembly, this positive feedback is not initiated without chromosomes. We propose that the dual detection of chromosomes and microtubules by the CPC is a critical step in assembling spindles around and only around chromosomes.

Publication types

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

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cell Nucleus / ultrastructure
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes / metabolism*
  • Chromosomes / ultrastructure
  • Female
  • Humans
  • Macromolecular Substances / metabolism
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Mitosis / physiology*
  • Polymers / metabolism
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism
  • Xenopus laevis

Substances

  • Chromosomal Proteins, Non-Histone
  • INCENP protein, Xenopus
  • Macromolecular Substances
  • Polymers
  • Xenopus Proteins
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases