Chromosome congression by Kinesin-5 motor-mediated disassembly of longer kinetochore microtubules

Cell. 2008 Nov 28;135(5):894-906. doi: 10.1016/j.cell.2008.09.046.

Abstract

During mitosis, sister chromatids congress to the spindle equator and are subsequently segregated via attachment to dynamic kinetochore microtubule (kMT) plus ends. A major question is how kMT plus-end assembly is spatially regulated to achieve chromosome congression. Here we find in budding yeast that the widely conserved kinesin-5 sliding motor proteins, Cin8p and Kip1p, mediate chromosome congression by suppressing kMT plus-end assembly of longer kMTs. Of the two, Cin8p is the major effector and its activity requires a functional motor domain. In contrast, the depolymerizing kinesin-8 motor Kip3p plays a minor role in spatial regulation of yeast kMT assembly. Our analysis identified a model where kinesin-5 motors bind to kMTs, move to kMT plus ends, and upon arrival at a growing plus end promote net kMT plus-end disassembly. In conclusion, we find that length-dependent control of net kMT assembly by kinesin-5 motors yields a simple and stable self-organizing mechanism for chromosome congression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromosomes, Fungal / metabolism
  • Green Fluorescent Proteins / metabolism
  • Kinesin / metabolism*
  • Kinetochores / metabolism*
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Molecular Motor Proteins
  • Mutation
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • CIN8 protein, S cerevisiae
  • KIP1 protein, S cerevisiae
  • KIP3 protein, S cerevisiae
  • Microtubule-Associated Proteins
  • Molecular Motor Proteins
  • Saccharomyces cerevisiae Proteins
  • Green Fluorescent Proteins
  • Kinesin