title: Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA. jstumpff@uvm.edu
authors.forename: Jason
authors.initials: J
authors.lastname: Stumpff
authors.forename: Michael
authors.initials: M
authors.lastname: Wagenbach
authors.forename: Andrew
authors.initials: A
authors.lastname: Franck
authors.forename: Charles L
authors.initials: CL
authors.lastname: Asbury
authors.forename: Linda
authors.initials: L
authors.lastname: Wordeman
mesh_terms: D045584:Chromosome Positioning / Q000502:physiology*; D002877:Chromosomes, Human / Q000378:metabolism*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D008954:Models, Biological; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: C502735:KIF18A protein, human; C484228:KIF4A protein, human; D016547:Kinesins