Motor-Independent Targeting of CLASPs to Kinetochores by CENP-E Promotes Microtubule Turnover and Poleward Flux

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 paralogue genes, clasp1...

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Bibliographic Details
Main Author: Maffini, S (author)
Other Authors: Maia, ARR (author), Manning, AL (author), Maliga, Z (author), Pereira, AL (author), Junqueira, M (author), Shevchenko, A (author), Hyman, A (author), Yates, JR (author), Galjart, N (author), Compton, DA (author), Maiato, H (author)
Format: article
Language:eng
Published: 2009
Subjects:
Flux
Kinetochores
Microtubule Turnover
Mitosis
Mitotic Spindle
Online Access:http://hdl.handle.net/10216/53558
Country:Portugal
Oai:oai:repositorio-aberto.up.pt:10216/53558
Description
Summary: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 paralogue 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 interactors of human CLASP1 using a proteomic approach. Among these, the microtubule plus-end directed motor CENP-E [5] was found to form a complex with CLASP1 that co-localizes to multiple structures of the mitotic apparatus in human cells. We found that CENP-E recruits both CLASP1 and CLASP2 to kinetochores independent of its motor activity or the presence of microtubules. Depletion of CLASPs or CENP-E by RNAi in human cells causes a significant and comparable reduction of kinetochore-microtubule poleward flux and turnover rates, as well as 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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