Author: ["Elsa Logarinho","Stefano Maffini","Marin Barisic","Andrea Marques","Alberto Toso","Patrick Meraldi","Helder Maiato"]
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Abstract
The formation of a bipolar spindle is critical for accurate segregation of the genome. Maiato and colleagues now demonstrate that CLASPs (cytoplasmic linker associated proteins) prevent spindle multipolarity in a manner independent of end-on kinetochore–microtubule attachments. They propose that CENP-E-mediated traction forces are balanced by CLASP-mediated recruitment of ninein to centriolar satellites. Loss of spindle-pole integrity during mitosis leads to multipolarity independent of centrosome amplification1,2,3,4. Multipolar-spindle conformation favours incorrect kinetochore–microtubule attachments, compromising faithful chromosome segregation and daughter-cell viability5,6. Spindle-pole organization influences and is influenced by kinetochore activity7,8, 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 multipolarity9,10,11,12,13. The first two reflect a role at the kinetochore–microtubule interface through interaction with specific kinetochore partners10,11,14, 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.Cite this article
Logarinho, E., Maffini, S., Barisic, M. et al. CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment. Nat Cell Biol 14, 295–303 (2012). https://doi.org/10.1038/ncb2423 