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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2009 arch     Display Documents



ID: 463208.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2009 arch
Motor-independent targeting of CLASPs to kinetochores by CENP-E promotes microtubule turnover and poleward flux
Authors:Maffini, Stefano; Maia, Ana R R; Manning, Amity L; Maliga, Zoltan; Pereira, Ana L; Junqueira, Magno; Shevchenko, Andrej; Hyman, Anthony; Yates, John R; Galjart, Niels; Compton, Duane A; Maiato, Helder
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Curr Biol
Volume:19
Issue / Number:18
Start Page:1566
End Page:1572
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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 interactors 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.
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:1337
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