Journal
DEVELOPMENTAL CELL
Volume 22, Issue 5, Pages 1017-1029Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2012.02.013
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Funding
- National Institutes of Health [GM69429, GM79373]
- National Science Foundation [1041173]
- Ruth L. Kirschstein National Service Award [GM778572]
- Leukemia and Lymphoma Society [3652-11]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1041173] Funding Source: National Science Foundation
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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.
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