A KID's game of tug o’ war

A hallmark of mitotic chromosome segregation is the aligning of chromosomes during metaphase. In order to position the duplicated genome at the ‘metaphase plate’, dividing cells utilize microtubule-based forces to push the chromosomes towards their central regions. The forces required to establish this arrangement of chromosomes at metaphase are the subject of two papers by Antonio et al.1xXkid, a chromokinesin required for chromosome alignment on the metaphase plate. Antonio, C. et al. Cell. 2000; 102: 425–435Abstract | Full Text | Full Text PDF | PubMedSee all References1 and Funabiki and Murray2xThe Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment and must be degraded to allow anaphase chromosome movement. Funabiki, H. and Murray, A.W. Cell. 2000; 102: 411–424Abstract | Full Text | Full Text PDF | PubMedSee all References2. Therein, the authors describe the role of the kinesin-like protein Xkid in generating the force responsible for chromosome congression during metaphase.Kid-like proteins were originally identified in Drosophila melanogaster in a screen for genes required for proper chromosome segregation during gametogenesis. One mutant gene, nod, encodes a protein with homology to the kinesin family of molecular motors. Later, a mammalian homologue, Kid (nesin-like ḎNA-binding protein), was discovered in a human carcinoma cell line. Consistent with a role in chromosome segregation, the human Kid protein was shown to localize along the length of chromosomes during M phase.The recent studies by these groups have further elucidated the mechanism by which Kid proteins contribute to chromosome segregation. Both groups cloned the Xenopus laevis homologue of Kid (Xkid), and, using the Xenopus egg extract system, they have shown that loss of Kid function leads to misalignment of chromosomes on the mitotic spindle during metaphase. Interestingly, this misalignment was due to the inability of chromosome arms to maintain their position at the metaphase plate: when antibodies against Xkid were added to metaphase-arrested extracts in which chromosomes had already aligned at the centre of the spindle, chromosome arms moved towards the poles independently of anaphase chromosome segregation.One consequence of the function of Xkid in maintaining chromosome position during metaphase is that it needs to be inactivated prior to anaphase so that chromosome segregation to the spindle poles can occur. In fact, Xkid is degraded by the anaphase-promoting complex/proteasome system at the onset of anaphase. Moreover, when a nondegradable form of Xkid was added to extracts, anaphase chromosome movement was inhibited.The findings in these two papers highlight several interesting aspects of mitotic spindle structure and function. Firstly, chromosome alignment during metaphase is not a static phenomenon; rather, it involves a balance of forces that act to push chromosomes towards the equator and pull them toward the poles. Secondly, the trigger for anaphase might actually be deactivation of the equatorial force, rather than the de novo activation of a poleward force. As such, the characterization of the Xkid motor sheds some light upon the process by which chromosomes undergo mitotic segregation in higher eukaryotes.