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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2009

Autores

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

Revista

Título: Current Biology

Vol. 19

Páginas: 1566-1572

ISSN: 0960-9822

Editora: Elsevier

Indexação

ISI Web of Knowledge - 86 Citações

Scopus - 91 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7