Multitasking Ska in Chromosome Segregation: Its Distinct Pools Might Specify Various Functions

Bioessays. 2018 Mar;40(3):10.1002/bies.201700176. doi: 10.1002/bies.201700176. Epub 2018 Jan 23.

Abstract

The human spindle and kinetochore associated (Ska) complex is required for proper mitotic progression. Extensive studies have demonstrated its important functions in both stable kinetochore-microtubule interactions and spindle checkpoint silencing. We suggest a model to explain how various Ska functions might be fulfilled by distinct pools of Ska at kinetochores. The Ndc80-loop pool of Ska is recruited by the Ndc80 loop, or together with some of its flanking sequences, and the recruitment is also dependent on Cdk1-mediated Ska3 phosphorylation. This pool seems to play a more important role in silencing the spindle checkpoint than stabilizing kinetochore-microtubule interactions. In contrast, the Ndc80-N-terminus pool of Ska is recruited by the N-terminal domains of Ndc80 and appears to be more important for stabilizing kinetochore-microtubule interactions. Here, we review and discuss the evidence that supports this model and suggest further experiments to test the functioning mechanisms of the Ska complex.

Keywords: Ndc80; Ska; kinetochore; microtubule; mitosis; spindle checkpoint.

Publication types

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

MeSH terms

  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle Proteins
  • Chromosome Segregation*
  • Cytoskeletal Proteins
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Kinetochores / metabolism*
  • Kinetochores / ultrastructure
  • M Phase Cell Cycle Checkpoints*
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Models, Biological
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Microtubule-Associated Proteins
  • NDC80 protein, human
  • Nuclear Proteins
  • Protein Isoforms
  • Ska3 protein, human
  • CDC2 Protein Kinase
  • CDK1 protein, human