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Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension.

TitleKif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension.
Publication TypeJournal Article
Year of Publication2012
AuthorsStumpff J, Wagenbach M, Franck A, Asbury CL, Wordeman L
JournalDevelopmental cell
Volume22
Issue5
Pagination1017-29
Date Published2012 May 15
ISSN1878-1551
KeywordsChromosome Positioning, Chromosomes, Human, HCT116 Cells, HeLa Cells, Humans, Kinesin, Kinetochores, Microtubules, Mitosis, Models, Biological, Spindle Apparatus
Abstract

<p>Alignment of chromosomes at the metaphase plate is a signature of cell division in metazoan cells, yet the mechanisms controlling this process remain ambiguous. Here we use a combination of quantitative live-cell imaging and reconstituted dynamic microtubule assays to investigate the molecular control of mitotic centromere movements. We establish that Kif18A (kinesin-8) attenuates centromere movement by directly promoting microtubule pausing in a concentration-dependent manner. This activity provides the dominant mechanism for restricting centromere movement to the spindle midzone. Furthermore, polar ejection forces spatially confine chromosomes via position-dependent regulation of kinetochore tension and centromere switch rates. We demonstrate that polar ejection forces are antagonistically modulated by chromokinesins. These pushing forces depend on Kid (kinesin-10) activity and are antagonized by Kif4A (kinesin-4), which functions to directly suppress microtubule growth. These data support a model in which Kif18A and polar ejection forces synergistically promote centromere alignment via spatial control of kinetochore-microtubule dynamics.</p>

DOI10.1016/j.devcel.2012.02.013
Alternate JournalDev. Cell