Functional studies on chromosome-associated microtubule dependent motors during cell division

Chromatin undergoes dramatic changes during the cell cycle. As the cell enters into M-phase chromatin condenses into chromosomes and the nuclear envelope breaks down. As the mitotic spindle start to form, chromosomes establish dynamic interactions with the microtubules. These interactions play an active role in spindle formation and are responsible for the movement of chromosomes that lead to their alignment on the metaphase plate and their segregation during anaphase.

Some of these interactions are mediated by chromokinesins, kinesin-like proteins that localize to the chromosome arms during M-phase. We have previously identified two of them in the Xenopus system: Xklp1 (Vernos et al., 1995; Walczak et al., 1998) and Xkid, (Antonio et al., 2000). To get a better understanding on Xklp1 function, we have examined the effect of Xklp1 depletion on spindle assembly in Xenopus egg extract. We found that in the absence of Xklp1 spindles form less efficiently and adopt a barrel-like shape due to an increase of the number of microtubules. Consistently an excess of Xklp1 in the egg extract resulted in the formation of spindles with reduced microtubule density. Similar results were obtained on centrosome nucleated microtubule asters (Castoldi M, VernosI.Mol Biol Cell. In Press). These results and the study of the Xklp1 motor domain in vitro (Bringmann et al, 2004) indicate that Xklp1 has unique properties and plays an important role for spindle assembly and function in the Xenopus egg extract system.

We found previously that Xkid has a very different function. It is required for chromosome alignment on the metaphase plate, (Antonio et al., 2000). In addition Xkid has a role in cell cycle progression during Xenopus oocyte meiotic maturation (Perez et al, 2002). We are currently trying to understand how a molecular motor may be required for meiotic cell cycle progression.