Aurora B is enriched at merotelic attachment sites, where it regulates MCAK.
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.
Knowlton
Anne Lide
AL
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Lan
Weijie
W
Stukenberg
P Todd
PT
D000818:Animals; D064127:Aurora Kinases; D002460:Cell Line; D016547:Kinesins / Q000378:metabolism / Q000502:physiology*; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D029867:Xenopus Proteins; C509242:mitotic centromere-associated kinesin, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins