page 613, Mazumdar et al. demonstrate that a human chromokinesin HKIF4A is needed to establish the correct condensation state of chromosomes.
Chromokinesins are localized along chromosome arms and are thought, at least in some cases, to act as part of the polar wind: they walk along microtubules away from centrosomes, thus dragging their chromosome cargos toward the middle of the mitotic spindle. The authors depleted HKIF4A from human fibroblast cells using antibodies and RNAi. They observed numerous mitotic defects including misaligned chromosomes, incomplete chromosome separation during anaphase, and disorganized spindles. The resulting daughter cells had a high rate of aneuploidy.
When the authors visually examined the chromosomes in RNAi-treated cells, they saw that chromosomes were hypercondensed relative to those in control cells. This was not due to an extended mitosis, as chromosomes of cells just entering mitosis were also hypercondensed. Furthermore, they found that HKIF4A interacts with the condensin complexes responsible for chromosome condensation.
Cells lacking HKIF4A had a diffuse rather than the normal axial localization of some condensin complex proteins. Thus, HKIF4A, having localized to chromosomes so that it can perhaps act as part of a polar wind, may use that localization to recruit or otherwise organize the condensins so that they can do their job. The more provocative possibility is that the kinesin motor itself is used to power a condensation event—a possibility that can be tested by injecting a kinase-dead mutant. The group also hopes to understand whether the segregation errors are triggered by the condensation problems, lack of motor function, or both. ▪