1992/01/01 by Yulia Steblyanko, Girish Rajendraprasad, Mariana Osswald +11 · 2 citations
Biochemistry, Genetics and Molecular Biology · Engineering · #Cellular Mechanics and Interactions #Microtubule and mitosis dynamics #Protist diversity and phylogeny #Transport and Logistics Innovations
paper · pdf · doi:10.15252/embj.2020105432
openalex publication_date 1992/01/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/23
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 of MT-dynamics in human cells to investigate the molecular mechanisms underlying MT-flux. We report that kinesin-7/CENP-E at kinetochores (KTs) is the predominant driver of MT-flux in early prometaphase, while kinesin-4/KIF4A on chromosome arms facilitates MT-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 the MT-flux driving force is transmitted from non-KT-MTs to KT-MTs by the MT couplers HSET and NuMA. Additionally, we found that the MT-flux rate correlates with spindle length, and this correlation depends on the establishment of stable end-on KT-MT attachments. Strikingly, we find that MT-flux is required to regulate spindle length by counteracting kinesin 13/MCAK-dependent MT-depolymerization. Thus, our study unveils the long-sought mechanism of MT-flux in human cells as relying on the coordinated action of four kinesins to compensate for MT-depolymerization and regulate spindle length.