Duplicated Chromosomes Are Aligned by Motors and Microtubule Dynamics

During prometaphase, the chromosomes come to lie at the midpoint between the two spindle poles, called the metaphase plate, in a process known as chromosome congression. During this process, bi-oriented chromosome pairs often oscillate backward and forward before arriving at the metaphase plate. Chromosome congression involves the coordinated activity of several microtubule-based motors together with regulators of microtubule assembly and disassembly (Figure 18-41b). These regulators are localized at the kinetochores, but how they are maintained there is poorly understood—they are not part of the stable kinetochore complexes described in the next section. The oscillating behavior of chromosomes involves lengthening of microtubules attached to one kinetochore and shortening of microtubules attached to the other kinetochore, all without losing their attachments. In metazoans, several microtubule-based motors associated with the kinetochore contribute to this process. First, dynein-dynactin provides the strongest force pulling the chromosome pair toward the more distant pole. This movement requires simultaneous shortening of the microtubule, which is enhanced by kinetochore-localized kinesin-13. The microtubules associated with the other kinetochore have to grow as the chromosome moves. Anchored at this kinetochore is the kinesin-related motor kinesin-7, which holds onto the growing (+) end of the lengthening microtubule. Also contributing to congression is another kinesin, chromokinesin/kinesin-4, which associates with the chromosome arms. Kinesin-4, a (+) end–directed motor, interacts with the polar microtubules to pull the chromosomes toward the center of the spindle. When the chromosomes have congressed to the metaphase plate, dynein-dynactin is released from the kinetochores and streams down the kinetochore microtubules to the poles. These different activities and opposing forces work together to bring all the chromosomes to the metaphase plate, at which point the cell is ready for anaphase.

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