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

Logarinho, Elsa
Maffini, Stefano
Barisic, Marin
Marques, Andrea
Toso, Alberto
Maiato, Helder
Published in Nature cell biology. 2012, vol. 14, no. 3, p. 295-303
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, WesternCell Line, TumorCentrosome/metabolism/physiologyChromosomal Proteins, Non-Histone/metabolism/physiologyChromosome Segregation/physiologyCytochalasin D/pharmacologyGreen Fluorescent Proteins/genetics/metabolismHeLa CellsHumansKinetochores/metabolism/physiologyMetaphase/physiologyMicroscopy, FluorescenceMicrotubule-Associated Proteins/genetics/metabolism/physiologyMitosis/physiologyMitotic Spindle Apparatus/drug effects/metabolism/physiologyModels, BiologicalRNA InterferenceTime-Lapse Imaging
PMID: 22307330
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Article (Published version) (2.7 MB) - public document Free access
Research group Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
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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

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Deposited on : 2013-07-09

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