Submitted by Linda-Wordeman on
Title | Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Stumpff J, Wagenbach M, Franck A, Asbury CL, Wordeman L |
Journal | Developmental cell |
Volume | 22 |
Issue | 5 |
Pagination | 1017-29 |
Date Published | 2012 May 15 |
ISSN | 1878-1551 |
Keywords | Chromosome 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> |
DOI | 10.1016/j.devcel.2012.02.013 |
Alternate Journal | Dev. Cell |