Mps1 kinase promotes sister-kinetochore bi-orientation by a tension-dependent mechanism

Curr Biol. 2007 Dec 18;17(24):2175-82. doi: 10.1016/j.cub.2007.11.032. Epub 2007 Nov 29.

Abstract

Segregation of sister chromatids to opposite spindle poles during anaphase is dependent on the prior capture of sister kinetochores by microtubules extending from opposite spindle poles (bi-orientation). If sister kinetochores attach to microtubules from the same pole (syntelic attachment), the kinetochore-spindle pole connections must be re-oriented to be converted to proper bi-orientation. This re-orientation is facilitated by Aurora B kinase (Ipl1 in budding yeast), which eliminates kinetochore-spindle pole connections that do not generate tension. Mps1 is another evolutionarily conserved protein kinase, required for spindle-assembly checkpoint and, in some organisms, for duplication of microtubule-organizing centers. Separately from these functions, however, Mps1 has an important role in chromosome segregation. Here we show that, in budding yeast, Mps1 has a crucial role in establishing sister-kinetochore bi-orientation on the mitotic spindle. Failure in bi-orientation with inactive Mps1 is not due to a lack of kinetochore-spindle pole connections by microtubules, but due to a defect in properly orienting the connections. Mps1 promotes re-orientation of kinetochore-spindle pole connections and eliminates those that do not generate tension between sister kinetochores. We did not find evidence that Ipl1 regulates Mps1 or vice versa; therefore, they play similar, but possibly independent, roles in facilitating bi-orientation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases
  • Intracellular Signaling Peptides and Proteins
  • Kinetochores / metabolism*
  • Metaphase / physiology*
  • Microtubules / metabolism
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomycetales
  • Spindle Apparatus / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Aurora Kinases
  • IPL1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • MPS1 protein, S cerevisiae