Dynein-dependent transport of spindle assembly checkpoint proteins off kinetochores toward spindle poles

FEBS Lett. 2014 Aug 25;588(17):3265-73. doi: 10.1016/j.febslet.2014.07.011. Epub 2014 Jul 23.

Abstract

A predominant mechanism of spindle assembly checkpoint (SAC) silencing is dynein-mediated transport of certain kinetochore proteins along microtubules. There are still conflicting data as to which SAC proteins are dynein cargoes. Using two ATP reduction assays, we found that the core SAC proteins Mad1, Mad2, Bub1, BubR1, and Bub3 redistributed from attached kinetochores to spindle poles, in a dynein-dependent manner. This redistribution still occurred in metaphase-arrested cells, at a time when the SAC should be satisfied and silenced. Unexpectedly, we found that a pool of Hec1 and Mis12 also relocalizes to spindle poles, suggesting KMN components as additional dynein cargoes. The potential significance of these results for SAC silencing is discussed.

Keywords: Bub1; Bub3; BubR1; Checkpoint silencing: cytoplasmic dynein; Hec1; Mad1; Mad2; Mis12; Mitotic checkpoint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Cycle Proteins / deficiency
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Dyneins / metabolism*
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • M Phase Cell Cycle Checkpoints*
  • Protein Transport
  • Spindle Poles / metabolism*

Substances

  • Cell Cycle Proteins
  • Adenosine Triphosphate
  • Dyneins