Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly

Dev Cell. 2007 Jan;12(1):31-43. doi: 10.1016/j.devcel.2006.11.001.

Abstract

Chromatin-induced spindle assembly depends on regulation of microtubule-depolymerizing proteins by the chromosomal passenger complex (CPC), consisting of Incenp, Survivin, Dasra (Borealin), and the kinase Aurora B, but the mechanism and significance of the spatial regulation of Aurora B activity remain unclear. Here, we show that the Aurora B pathway is suppressed in the cytoplasm of Xenopus egg extract by phosphatases, but that it becomes activated by chromatin via a Ran-independent mechanism. While spindle microtubule assembly normally requires Dasra-dependent chromatin binding of the CPC, this function of Dasra can be bypassed by clustering Aurora B-Incenp by using anti-Incenp antibodies, which stimulate autoactivation among bound complexes. However, such chromatin-independent Aurora B pathway activation promotes centrosomal microtubule assembly and produces aberrant achromosomal spindle-like structures. We propose that chromosomal enrichment of the CPC results in local kinase autoactivation, a mechanism that contributes to the spatial regulation of spindle assembly and possibly to other mitotic processes.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / immunology
  • Aurora Kinases
  • Cell Extracts
  • Centrosome / metabolism
  • Chromosomal Proteins, Non-Histone / immunology
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes / metabolism*
  • Enzyme Activation
  • Histones / metabolism
  • Microtubules / metabolism
  • Ovum
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / chemistry
  • Spindle Apparatus / metabolism*
  • Stathmin / metabolism
  • Xenopus / metabolism*
  • Xenopus Proteins / immunology
  • Xenopus Proteins / metabolism
  • ran GTP-Binding Protein / metabolism

Substances

  • Antibodies
  • CDCA8 protein, Xenopus
  • Cell Extracts
  • Chromosomal Proteins, Non-Histone
  • Histones
  • INCENP protein, Xenopus
  • Stathmin
  • Xenopus Proteins
  • cdca9 protein, Xenopus
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • ran GTP-Binding Protein