Aurora B controls kinetochore-microtubule attachments by inhibiting Ska complex-KMN network interaction

J Cell Biol. 2012 Mar 5;196(5):563-71. doi: 10.1083/jcb.201109001. Epub 2012 Feb 27.

Abstract

The KMN network (named according to the acronym for KNL1, Mis12, and Ndc80) and the more recently identified Ska complex (Ska1-3) have been shown to mediate kinetochore (KT)-microtubule (MT) attachments. How these two complexes cooperate to achieve stable end-on attachments remains unknown. In this paper, we show that Aurora B negatively regulates the localization of the Ska complex to KTs and that recruitment of the Ska complex to KTs depends on the KMN network. We identified interactions between members of the KMN and Ska complexes and demonstrated that these interactions are regulated by Aurora B. Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cytoskeletal Proteins
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Mitosis / physiology
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Cytoskeletal Proteins
  • DSN1 protein, human
  • Knl1 protein, human
  • Microtubule-Associated Proteins
  • NDC80 protein, human
  • Nuclear Proteins
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • SKA1 protein, human
  • SKA2 protein, human
  • Ska3 protein, human
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases