Department of Physics, Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Nat Cell Biol. 2011 May 22;13(7):846-52. doi: 10.1038/ncb2256.
During cell division the replicated chromosomes are segregated precisely towards the spindle poles. Although many cellular processes involving motility require ATP-fuelled force generation by motor proteins, most models of the chromosome movement invoke the release of energy stored at strained (owing to GTP hydrolysis) plus ends of microtubules. This energy is converted into chromosome movement through passive couplers, whereas the role of molecular motors is limited to the regulation of microtubule dynamics. Here we report, that the microtubule-depolymerizing activity of MCAK (mitotic centromere-associated kinesin), the founding member of the kinesin-13 family, is accompanied by the generation of significant tension-remarkably, at both microtubule ends. An MCAK-decorated bead strongly attaches to the microtubule side, but readily slides along it in either direction under weak external loads and tightly captures and disassembles both microtubule ends. We show that the depolymerization force increases with the number of interacting MCAK molecules and is ∼1 pN per motor. These results provide a simple model for the generation of driving force and the regulation of chromosome segregation by the activity of MCAK at both kinetochores and spindle poles through a 'side-sliding, end-catching' mechanism.
在细胞分裂过程中，复制的染色体精确地向纺锤体两极分离。尽管涉及运动的许多细胞过程都需要由马达蛋白驱动的 ATP 供能的力生成，但大多数染色体运动模型都利用微管末端的张力（由于 GTP 水解）释放能量。这种能量通过被动偶联器转化为染色体运动，而分子马达的作用仅限于调节微管动力学。在这里，我们报告说，微管解聚酶 MCAK（有丝分裂着丝粒相关驱动蛋白）的微管解聚活性伴随着显著张力的产生——在微管两端都很明显。一个被 MCAK 修饰的珠子强烈地附着在微管的一侧，但在外部负载较弱的情况下，它很容易向任意方向滑动，并且紧紧地捕获和拆卸微管的两端。我们表明，解聚力随相互作用的 MCAK 分子数量的增加而增加，每个马达约为 1 pN。这些结果提供了一个简单的模型，用于通过“侧滑、端捕获”机制，由 MCAK 在动粒和纺锤体两极的活性产生驱动力并调节染色体分离。
