Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment

Dev Cell. 2011 Mar 15;20(3):342-52. doi: 10.1016/j.devcel.2011.01.008.

Abstract

Proper bipolar attachment of sister kinetochores to the mitotic spindle is critical for accurate chromosome segregation in mitosis. Here we show an essential role of the formin mDia3 in achieving metaphase chromosome alignment. This function is independent of mDia3 actin nucleation activity, but is attributable to EB1-binding by mDia3. Furthermore, the microtubule binding FH2 domain of mDia3 is phosphorylated by Aurora B kinase in vitro, and cells expressing the nonphosphorylatable mDia3 mutant cannot position chromosomes at the metaphase plate. Purified recombinant mDia3 phosphorylated by Aurora B exhibits reduced ability to bind microtubules and stabilize microtubules against cold-induced disassembly in vitro. Cells expressing the phosphomimetic mDia3 mutant do not form stable kinetochore microtubule fibers; despite they are able to congress chromosomes to the metaphase plate. These findings reveal a key role for mDia3 and its regulation by Aurora B phosphorylation in achieving proper stable kinetochore microtubule attachment.

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Aurora Kinase B
  • Aurora Kinases
  • Chromosome Segregation
  • Chromosomes / metabolism*
  • Chromosomes / ultrastructure
  • Formins
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Metaphase / physiology*
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / metabolism

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • DIAPH3 protein, human
  • EB1 microtubule binding proteins
  • Formins
  • Microtubule-Associated Proteins
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases