Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment

Dev Cell. 2017 Sep 25;42(6):640-654.e5. doi: 10.1016/j.devcel.2017.08.022.

Abstract

The chromosomal passenger complex (CPC) localizes to centromeres in early mitosis to activate its subunit Aurora B kinase. However, it is unclear whether centromeric CPC localization contributes to CPC functions beyond Aurora B activation. Here, we show that an activated CPC that cannot localize to centromeres supports functional assembly of the outer kinetochore but is unable to correct errors in kinetochore-microtubule attachment in Xenopus egg extracts. We find that CPC has two distinct roles at centromeres: one to selectively phosphorylate Ndc80 to regulate attachment and a second, conserved kinase-independent role in the proper composition of inner kinetochore proteins. Although a fully assembled inner kinetochore is not required for outer kinetochore assembly, we find it is essential to recruit tension indicators, such as BubR1 and 3F3/2, to erroneous attachments. We conclude centromeric CPC is necessary for tension-dependent removal of erroneous attachments and for the kinetochore composition required to detect tension loss.

Keywords: Aurora B kinase; CCAN; cell division; centromeres; chromatin; chromosomal passenger complex; error correction; kinetochores; microtubules; tension sensing.

MeSH terms

  • Animals
  • Aurora Kinase B / metabolism
  • Centromere / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cytoskeletal Proteins
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Microtubules / metabolism*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Xenopus

Substances

  • Chromosomal Proteins, Non-Histone
  • Cytoskeletal Proteins
  • NDC80 protein, human
  • Nuclear Proteins
  • Aurora Kinase B
  • BUB1 protein, human
  • Protein Serine-Threonine Kinases