CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment

Nat Cell Biol. 2012 Feb 5;14(3):295-303. doi: 10.1038/ncb2423.


Loss of spindle-pole integrity during mitosis leads to multipolarity independent of centrosome amplification. Multipolar-spindle conformation favours incorrect kinetochore-microtubule attachments, compromising faithful chromosome segregation and daughter-cell viability. Spindle-pole organization influences and is influenced by kinetochore activity, but the molecular nature behind this critical force balance is unknown. CLASPs are microtubule-, kinetochore- and centrosome-associated proteins whose functional perturbation leads to three main spindle abnormalities: monopolarity, short spindles and multipolarity. The first two reflect a role at the kinetochore-microtubule interface through interaction with specific kinetochore partners, but how CLASPs prevent spindle multipolarity remains unclear. Here we found that human CLASPs ensure spindle-pole integrity after bipolarization in response to CENP-E- and Kid-mediated forces from misaligned chromosomes. This function is independent of end-on kinetochore-microtubule attachments and involves the recruitment of ninein to residual pericentriolar satellites. Distinctively, multipolarity arising through this mechanism often persists through anaphase. We propose that CLASPs and ninein confer spindle-pole resistance to traction forces exerted during chromosome congression, thereby preventing irreversible spindle multipolarity and aneuploidy.

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Centrosome / metabolism
  • Centrosome / physiology
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomal Proteins, Non-Histone / physiology*
  • Chromosome Segregation / physiology
  • Cytochalasin D / pharmacology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Kinetochores / physiology
  • Metaphase / physiology*
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Mitosis / physiology
  • Models, Biological
  • RNA Interference
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology*
  • Time-Lapse Imaging


  • CLASP1 protein, human
  • CLASP2 protein, human
  • Chromosomal Proteins, Non-Histone
  • Microtubule-Associated Proteins
  • centromere protein E
  • Green Fluorescent Proteins
  • Cytochalasin D