The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly

Cell. 2004 Jul 23;118(2):187-202. doi: 10.1016/j.cell.2004.06.026.

Abstract

In cells lacking centrosomes, such as those found in female meiosis, chromosomes must nucleate and stabilize microtubules in order to form a bipolar spindle. Here we report the identification of Dasra A and Dasra B, two new components of the vertebrate chromosomal passenger complex containing Incenp, Survivin, and the kinase Aurora B, and demonstrate that this complex is required for chromatin-induced microtubule stabilization and spindle formation. The failure of microtubule stabilization caused by depletion of the chromosomal passenger complex was rescued by codepletion of the microtubule-depolymerizing kinesin MCAK, whose activity is negatively regulated by Aurora B. By contrast, we present evidence that the Ran-GTP pathway of chromatin-induced microtubule nucleation does not require the chromosomal passenger complex, indicating that the mechanisms of microtubule assembly by these two pathways are distinct. We propose that the chromosomal passenger complex regulates local MCAK activity to permit spindle formation via stabilization of chromatin-associated microtubules.

Publication types

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

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Base Sequence / genetics
  • Cell Division / physiology
  • Cell Extracts
  • Centromere / genetics
  • Centromere / metabolism
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / isolation & purification
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Structures / genetics
  • Chromosome Structures / metabolism*
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • HeLa Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Kinesin / genetics
  • Kinesin / metabolism
  • Macromolecular Substances
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Sequence Homology, Nucleic Acid
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*
  • Survivin
  • Xenopus
  • Xenopus Proteins / genetics
  • Xenopus Proteins / isolation & purification
  • Xenopus Proteins / metabolism*
  • ran GTP-Binding Protein / genetics
  • ran GTP-Binding Protein / metabolism

Substances

  • BIRC5 protein, human
  • CDCA8 protein, Xenopus
  • Cell Extracts
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA, Complementary
  • INCENP protein, human
  • Inhibitor of Apoptosis Proteins
  • KIF2C protein, human
  • Macromolecular Substances
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • Xenopus Proteins
  • cdca9 protein, Xenopus
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Kinesin
  • ran GTP-Binding Protein

Associated data

  • GENBANK/AY644400
  • GENBANK/AY644401