Journal
CURRENT BIOLOGY
Volume 19, Issue 18, Pages 1566-1572Publisher
CELL PRESS
DOI: 10.1016/j.cub.2009.07.059
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Funding
- Fundacao para a Ciencia e a Tecnologia (FCT) of Portugal [SFRH/BPD/26780/2006, SFRH/BD/32976/2006, SFRH/BD/25084/2005, PTDC/BIA-BCM/66106/2006, PTDC/SAUOBD/66113/2006]
- National Institutes of Health [GM51542]
- Gulbenkian Programme on the Frontiers in Life Sciences
- Fundação para a Ciência e a Tecnologia [SFRH/BD/25084/2005, PTDC/BIA-BCM/66106/2006, SFRH/BPD/26780/2006, SFRH/BD/32976/2006] Funding Source: FCT
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Efficient chromosome segregation during mitosis relies on the coordinated activity of molecular motors with proteins that regulate kinetochore attachments to dynamic spindle microtubules [1]. CLASPs are conserved kinetochore- and microtubule-associated proteins encoded by two paralog genes, clasp1 and clasp2, and have been previously implicated in the regulation of kinetochore microtubule dynamics [2-4]. However, it remains unknown how CLASPs work in concert with other proteins to form a functional kinetochore microtubule interface. Here we have identified mitotic inter-actors of human CLASP1 via a proteomic approach. Among these, the microtubule plus-end-directed motor CENP-E [5] was found to form a complex with CLASP1 that colocalizes to multiple structures of the mitotic apparatus in human cells. We found that CENP-E recruits both CLASP1 and CLASP2 to kinetochores independently of its motor activity or the presence of microtubules. Depletion of CLASPs or CENP-E by RNA interference in human cells causes a significant and comparable reduction of kinetochore microtubule poleward flux and turnover rates and rescues spindle bipolarity in Kif2a-depleted cells. We conclude that CENP-E integrates two critical functions that are important for accurate chromosome movement and spindle architecture: one relying directly on its motor activity, and the other involving the targeting of key microtubule regulators to kinetochores.
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