Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control

Nat Cell Biol. 2013 Aug;15(8):948-57. doi: 10.1038/ncb2801. Epub 2013 Jul 14.

Abstract

Molecular motors play critical roles in the formation of mitotic spindles, either through controlling the stability of individual microtubules, or by crosslinking and sliding microtubule arrays. Kinesin-8 motors are best known for their regulatory roles in controlling microtubule dynamics. They contain microtubule-destabilizing activities, and restrict spindle length in a wide variety of cell types and organisms. Here, we report an antiparallel microtubule-sliding activity of the budding yeast kinesin-8, Kip3. The in vivo importance of this sliding activity was established through the identification of complementary Kip3 mutants that separate the sliding activity and microtubule-destabilizing activity. In conjunction with Cin8, a kinesin-5 family member, the sliding activity of Kip3 promotes bipolar spindle assembly and the maintenance of genome stability. We propose a slide-disassemble model where the sliding and destabilizing activity of Kip3 balance during pre-anaphase. This facilitates normal spindle assembly. However, the destabilizing activity of Kip3 dominates in late anaphase, inhibiting spindle elongation and ultimately promoting spindle disassembly.

Publication types

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

MeSH terms

  • Blotting, Western
  • Genomic Instability
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Microtubules / metabolism*
  • Models, Biological
  • Mutation
  • Organelle Size
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spindle Apparatus / metabolism*

Substances

  • CIN8 protein, S cerevisiae
  • KIP3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Kinesin