Aurora B kinase controls the targeting of the Astrin-SKAP complex to bioriented kinetochores

J Cell Biol. 2010 Oct 18;191(2):269-80. doi: 10.1083/jcb.201006129. Epub 2010 Oct 11.

Abstract

During mitosis, kinetochores play multiple roles to generate interactions with microtubules, and direct chromosome congression, biorientation, error correction, and anaphase segregation. However, it is unclear what changes at the kinetochore facilitate these distinct activities. Here, we describe a complex of the spindle- and kinetochore-associated protein Astrin, the small kinetochore-associated protein (SKAP), and the dynein light chain LC8. Although most dynein-associated proteins localize to unaligned kinetochores in an Aurora B-dependent manner, Astrin, SKAP, and LC8 localization is antagonized by Aurora B such that they target exclusively to bioriented kinetochores. Astrin-SKAP-depleted cells fail to maintain proper chromosome alignment, resulting in a spindle assembly checkpoint-dependent mitotic delay. Consistent with a role in stabilizing bioriented attachments, Astrin and SKAP bind directly to microtubules and are required for CLASP localization to kinetochores. In total, our results suggest that tension-dependent Aurora B phosphorylation can act to control outer kinetochore composition to provide distinct activities to prometaphase and metaphase kinetochores.

Publication types

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

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Chickens
  • Cytoplasmic Dyneins / metabolism*
  • Dyneins / metabolism
  • Humans
  • Kinetochores / metabolism*
  • Metaphase
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Mitosis / physiology
  • Phosphorylation
  • Protein Subunits / metabolism
  • Protein Transport
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*

Substances

  • CLASP1 protein, human
  • CLASP2 protein, human
  • Cell Cycle Proteins
  • KNSTRN protein, human
  • Microtubule-Associated Proteins
  • Protein Subunits
  • SPAG5 protein, human
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • DYNLL1 protein, human
  • Cytoplasmic Dyneins
  • Dyneins