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Nat Cell Biol. 2014 Dec;16(12):1249-56. doi: 10.1038/ncb3060. Epub 2014 Nov 10.

Kinetochore motors drive congression of peripheral polar chromosomes by overcoming random arm-ejection forces.

Author information

1
Chromosome Instability and Dynamics Laboratory, Institute for Molecular and Cell Biology, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
2
Instituto de Engenharia Biom├ędica, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
3
Biocenter, Division of Molecular Pathophysiology, Innsbruck Medical University, Innrain 80, 6020 Innsbruck, Austria.
4
1] Chromosome Instability and Dynamics Laboratory, Institute for Molecular and Cell Biology, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal [2] Cell Division Unit, Department of Experimental Biology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.

Abstract

Accurate chromosome segregation during cell division in metazoans relies on proper chromosome congression at the equator. Chromosome congression is achieved after bi-orientation to both spindle poles shortly after nuclear envelope breakdown, or by the coordinated action of motor proteins that slide misaligned chromosomes along pre-existing spindle microtubules. These proteins include the minus-end-directed kinetochore motor dynein, and the plus-end-directed motors CENP-E at kinetochores and chromokinesins on chromosome arms. However, how these opposite and spatially distinct activities are coordinated to drive chromosome congression remains unknown. Here we used RNAi, chemical inhibition, kinetochore tracking and laser microsurgery to uncover the functional hierarchy between kinetochore and arm-associated motors, exclusively required for congression of peripheral polar chromosomes in human cells. We show that dynein poleward force counteracts chromokinesins to prevent stabilization of immature/incorrect end-on kinetochore-microtubule attachments and random ejection of polar chromosomes. At the poles, CENP-E becomes dominant over dynein and chromokinesins to bias chromosome ejection towards the equator. Thus, dynein and CENP-E at kinetochores drive congression of peripheral polar chromosomes by preventing arm-ejection forces mediated by chromokinesins from working in the wrong direction.

PMID:
25383660
DOI:
10.1038/ncb3060
[Indexed for MEDLINE]
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