Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins.
kinesins
kinetochore
microtubules
mitosis
mitotic spindle
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
27
04
2020
revised:
24
09
2020
accepted:
25
09
2020
pubmed:
20
10
2020
medline:
13
4
2021
entrez:
19
10
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33073400
doi: 10.15252/embj.2020105432
pmc: PMC7705458
doi:
Substances chimiques
Cell Cycle Proteins
0
KIF15 protein, human
0
NUMA1 protein, human
0
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e105432Subventions
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R215-2015-4081
Organisme : Kraeftens Bekaempelse (DCS)
ID : R146-A9322
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
ID : 681443
Organisme : Novo Nordisk Fonden (NNF)
ID : NNF19OC0058504
Informations de copyright
© 2020 The Authors.
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