Aurora B is enriched at merotelic attachment sites, where it regulates MCAK

Curr Biol. 2006 Sep 5;16(17):1705-10. doi: 10.1016/j.cub.2006.07.057.

Abstract

Kinetochores often form merotelic attachments, in which a single kinetochore is attached to microtubules from both spindle poles. These attachments can result in improper chromosome segregation and are a significant source of aneuploidy, a hallmark of cancer. Aurora B kinase and the kinesin-13 microtubule depolymerase mitotic-centromere-associated kinesin (MCAK) are required to release improper microtubule attachments. Aurora B regulates MCAK's activity and localization. We set out to understand why MCAK and Aurora B are more abundant at some metaphase-aligned centromeres but are present at low amounts on most others. We found that members of the Aurora B complex are specifically enriched at merotelic attachment sites. We also found that Aurora B does not require its activity to become enriched at these sites; however, inhibition of Aurora B activity causes a significant increase in the number of merotelic attachments per cell. Aurora B activity enriches MCAK at merotelic attachments and phosphorylates MCAK on residues that regulate its microtubule depolymerase activity. These data demonstrate that proteins that resolve the defect are specifically localized to merotelic attachments, where their enzymatic activities are regulated.

Publication types

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

MeSH terms

  • Animals
  • Aurora Kinases
  • Cell Line
  • Kinesin / metabolism
  • Kinesin / physiology*
  • Kinetochores / metabolism*
  • Microtubules / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Spindle Apparatus / metabolism
  • Xenopus Proteins / metabolism
  • Xenopus Proteins / physiology*
  • Xenopus laevis

Substances

  • Xenopus Proteins
  • mitotic centromere-associated kinesin, Xenopus
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Kinesin