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

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Maffini, S (Author) Other; Maia, ARR (Author) Other; Manning, AL (Author) Other; Maliga, Z (Author) Other; Pereira, AL (Author) Other; Junqueira, M (Author) Other; Shevchenko, A (Author) Other; Hyman, A (Author) Other; Yates, JR (Author) Other; Galjart, N (Author) Other; Compton, DA (Author) Other; Helder Maiato (Author) FMUP

Journal

Title: Current Biology

Vol. 19

Pages: 1566-1572

ISSN: 0960-9822

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 86 Citations

Scopus - 91 Citations

Other information

Authenticus ID: P-003-FQ4

DOI: 10.1016/j.cub.2009.07.059

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7