Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

Steblyanko, Y (Autor) Outra; Rajendraprasad, G (Autor) Outra; Osswald, M (Autor) Outra; Eibes, S (Autor) Outra; Jacome, A (Autor) Outra; Geley, S (Autor) Outra; Pereira, AJ (Autor) Outra; Helder Maiato (Autor) FMUP; Barisic, M (Autor) Outra

Revista

Título: EMBO Journal

Vol. 39

ISSN: 0261-4189

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 1 Citação

Scopus - 18 Citações

Outras Informações

ID Authenticus: P-00S-XAN

DOI: 10.15252/embj.2020105432

Abstract (EN): Mitotic spindle microtubules (MTs) undergo continuous poleward flux, whose driving force and function in humans remain unclear. Here, we combined loss-of-function screenings with analysis ofMT-dynamics in human cells to investigate the molecular mechanisms underlyingMT-flux. We report that kinesin-7/CENP-E at kinetochores (KTs) is the predominant driver ofMT-flux in early prometaphase, while kinesin-4/KIF4A on chromosome arms facilitatesMT-flux during late prometaphase and metaphase. Both these activities work in coordination with kinesin-5/EG5 and kinesin-12/KIF15, and our data suggest that theMT-flux driving force is transmitted from non-KT-MTs toKT-MTs by theMTcouplersHSETand NuMA. Additionally, we found that theMT-flux rate correlates with spindle length, and this correlation depends on the establishment of stable end-onKT-MTattachments. Strikingly, we find thatMT-flux is required to regulate spindle length by counteracting kinesin 13/MCAK-dependentMT-depolymerization. Thus, our study unveils the long-sought mechanism ofMT-flux in human cells as relying on the coordinated action of four kinesins to compensate forMT-depolymerization and regulate spindle length.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 22