Chromatids segregate without centrosomes during Caenorhabditis elegans mitosis in a Ran- and CLASP-dependent manner

Mol Biol Cell. 2015 Jun 1;26(11):2020-9. doi: 10.1091/mbc.E14-12-1577. Epub 2015 Apr 1.

Abstract

During mitosis, chromosomes are connected to a microtubule-based spindle. Current models propose that displacement of the spindle poles and/or the activity of kinetochore microtubules generate mechanical forces that segregate sister chromatids. Using laser destruction of the centrosomes during Caenorhabditis elegans mitosis, we show that neither of these mechanisms is necessary to achieve proper chromatid segregation. Our results strongly suggest that an outward force generated by the spindle midzone, independently of centrosomes, is sufficient to segregate chromosomes in mitotic cells. Using mutant and RNAi analysis, we show that the microtubule-bundling protein SPD-1/MAP-65 and BMK-1/kinesin-5 act as a brake opposing the force generated by the spindle midzone. Conversely, we identify a novel role for two microtubule-growth and nucleation agents, Ran and CLASP, in the establishment of the centrosome-independent force during anaphase. Their involvement raises the interesting possibility that microtubule polymerization of midzone microtubules is continuously required to sustain chromosome segregation during mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromatids
  • Chromosome Segregation*
  • Kinesins / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Mitosis* / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • RNA Interference
  • Spindle Apparatus / metabolism*
  • ran GTP-Binding Protein

Substances

  • CLS-2 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Microtubule-Associated Proteins
  • SPD-1 protein, C elegans
  • BMK-1 protein, C elegans
  • Kinesins
  • Monomeric GTP-Binding Proteins
  • RAN-1 protein, C elegans
  • ran GTP-Binding Protein