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

• Type: Article in International Scientific Journal
• Date: 2020

Authors

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

Journal

Title: EMBO Journal

Vol. 39

ISSN: 0261-4189

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 18 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 22