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Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis

Wandke, Cornelia
Barisic, Marin
Sigl, Reinhard
Rauch, Veronika
Wolf, Frank
Amaro, Ana C
Pereira, Antonio J
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Published in The Journal of cell biology. 2012, vol. 198, no. 5, p. 847-63
Abstract Chromokinesins are microtubule plus end-directed motor proteins that bind to chromosome arms. In Xenopus egg cell-free extracts, Xkid and Xklp1 are essential for bipolar spindle formation but the functions of the human homologues, hKID (KIF22) and KIF4A, are poorly understood. By using RNAi-mediated protein knockdown in human cells, we find that only co-depletion delayed progression through mitosis in a Mad2-dependent manner. Depletion of hKID caused abnormal chromosome arm orientation, delayed chromosome congression, and sensitized cells to nocodazole. Knockdown of KIF4A increased the number and length of microtubules, altered kinetochore oscillations, and decreased kinetochore microtubule flux. These changes were associated with failures in establishing a tight metaphase plate and an increase in anaphase lagging chromosomes. Co-depletion of both chromokinesins aggravated chromosome attachment failures, which led to mitotic arrest. Thus, hKID and KIF4A contribute independently to the rapid and correct attachment of chromosomes by controlling the positioning of chromosome arms and the dynamics of microtubules, respectively.
Keywords Anaphase/physiologyAnimalsCalcium-Binding Proteins/metabolismCell Cycle Checkpoints/physiologyCell Cycle Proteins/metabolismCell LineCell Line, TumorChromosome Segregation/physiologyDNA-Binding Proteins/metabolismHCT116 CellsHEK293 CellsHeLa CellsHumansKinesin/metabolismKinetochores/metabolismMetaphase/physiologyMicrotubules/metabolismMitosis/physiologyMitotic Spindle Apparatus/metabolismNuclear Proteins/metabolismRepressor Proteins/metabolismXenopusXenopus Proteins/metabolism
PMID: 22945934
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Research group Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
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WANDKE, Cornelia et al. Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis. In: The Journal of cell biology, 2012, vol. 198, n° 5, p. 847-63. doi: 10.1083/jcb.201110060 https://archive-ouverte.unige.ch/unige:28854

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Deposited on : 2013-07-09

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