Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis

Abstract

Human chromokinesins hKID and KIF4A contribute to proper attachment of chromosomes by controlling the positioning of the chromosome arms and microtubule dynamics, respectively.

Prime movers: the mechanochemistry of mitotic kinesins

“…This force is thought to be mediated by the polymerization of microtubules against the chromosome and by chromosome-bound motors known as chromokinesins [G] (for review see 132 ). Of these, KIF22 (also known as NOD or KID), a member of the kinesin-10 family, is the most likely mediator of the polar ejection force 133 , although the extent to which KIF22 contributes to chromosome congression is unclear 112,[133][134][135][136][137][138] . Optical trapping microscopy shows KIF22 to be a non-processive motor that steps towards the microtubule plus-end, consistent with a role in mediating the ejection force 139 .…”

“…Optical trapping microscopy shows KIF22 to be a non-processive motor that steps towards the microtubule plus-end, consistent with a role in mediating the ejection force 139 . However, there is no strong evidence that these motors contribute to the polar ejection force 133,134 . In fact, it is has been proposed that they may counteract this force by suppressing spindle microtubule dynamics 112 .…”

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

“…5 Dynein achieves this by counteracting PEFs generated mainly by the microtubule plus-end directed motor proteins chromokinesins. [25][26][27][28][29][30][31][32] Co-depletion of CENP-E and Dynein in live U2OS cells stably expressing H2B-GFP and mCherry-a-tubulin to simultaneously visualize chromosomes and microtubules, respectively, led to the ejection of polar chromosomes from spindle poles and stabilization of their kinetochore-microtubule attachments. 5 This was opposite from the behavior of chromosomes that remained locked at the poles and lacked stable end-on kinetochore-microtubule attachments in CENP-E inhibited cells, in which Dynein function was left intact.…”

“…This initial poleward movement depends on the microtubule minus-enddirected motor Dynein at unattached kinetochores, [14][15][16]43,44 whereas the subsequent motion toward the equator depends on the microtubule plus-end-directed motor proteins CENP-E at kinetochores 20 and chromokinesins on chromosome arms. 25,27,28 We sought to investigate whether the dependence on motor proteins for chromosome congression correlates with chromosome positioning at NEB. To address this, we generated a stable U2OS cell line expressing GFP-CENP-A and mCherry-a-tubulin, which allowed us to track kinetochore positions relative to the mitotic spindle using high-resolution live-cell imaging.…”

“…24 Additional studies revealed that these forces are mainly generated by the microtubule plus-end-directed motor proteins chromokinesins. [25][26][27][28][29][30][31][32] During the coordinated action of all these motor activities that mediate chromosome congression it is crucial to prevent and/or correct potential erroneous kinetochore-microtubule attachments. Syntelic attachments occur when both sister kinetochores become attached by microtubules originated from a single pole, while merotelic attachments arise when a single kinetochore becomes attached to both spindle poles.…”