en
Scientific article
Open access
English

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

Published inNature cell biology, vol. 14, no. 3, p. 295-303
Publication date2012
Abstract

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.

Keywords
  • Blotting, Western
  • Cell Line, Tumor
  • Centrosome/metabolism/physiology
  • Chromosomal Proteins, Non-Histone/metabolism/physiology
  • Chromosome Segregation/physiology
  • Cytochalasin D/pharmacology
  • Green Fluorescent Proteins/genetics/metabolism
  • HeLa Cells
  • Humans
  • Kinetochores/metabolism/physiology
  • Metaphase/physiology
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins/genetics/metabolism/physiology
  • Mitosis/physiology
  • Mitotic Spindle Apparatus/drug effects/metabolism/physiology
  • Models, Biological
  • RNA Interference
  • Time-Lapse Imaging
Affiliation Not a UNIGE publication
Citation (ISO format)
LOGARINHO, Elsa et al. CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment. In: Nature cell biology, 2012, vol. 14, n° 3, p. 295–303. doi: 10.1038/ncb2423
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1465-7392
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464downloads

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