Gardner Melissa K, Bouck David C, Paliulis Leocadia V, Meehl Janet B, O'Toole Eileen T, Haase Julian, Soubry Adelheid, Joglekar Ajit P, Winey Mark, Salmon Edward D, Bloom Kerry, Odde David J
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Cell. 2008 Nov 28;135(5):894-906. doi: 10.1016/j.cell.2008.09.046.
During mitosis, sister chromatids congress to the spindle equator and are subsequently segregated via attachment to dynamic kinetochore microtubule (kMT) plus ends. A major question is how kMT plus-end assembly is spatially regulated to achieve chromosome congression. Here we find in budding yeast that the widely conserved kinesin-5 sliding motor proteins, Cin8p and Kip1p, mediate chromosome congression by suppressing kMT plus-end assembly of longer kMTs. Of the two, Cin8p is the major effector and its activity requires a functional motor domain. In contrast, the depolymerizing kinesin-8 motor Kip3p plays a minor role in spatial regulation of yeast kMT assembly. Our analysis identified a model where kinesin-5 motors bind to kMTs, move to kMT plus ends, and upon arrival at a growing plus end promote net kMT plus-end disassembly. In conclusion, we find that length-dependent control of net kMT assembly by kinesin-5 motors yields a simple and stable self-organizing mechanism for chromosome congression.
在有丝分裂过程中,姐妹染色单体汇聚到纺锤体赤道面,随后通过附着于动态动粒微管(kMT)正端而被分离。一个主要问题是kMT正端组装如何在空间上受到调控以实现染色体汇聚。在这里,我们在芽殖酵母中发现,广泛保守的驱动蛋白-5滑动运动蛋白Cin8p和Kip1p通过抑制较长kMT的kMT正端组装来介导染色体汇聚。在这两者中,Cin8p是主要效应因子,其活性需要一个功能性的运动结构域。相比之下,解聚驱动蛋白-8运动蛋白Kip3p在酵母kMT组装的空间调控中起次要作用。我们的分析确定了一个模型,其中驱动蛋白-5运动蛋白结合到kMT上,移动到kMT正端,并在到达生长中的正端时促进kMT正端的净解聚。总之,我们发现驱动蛋白-5运动蛋白对kMT组装的长度依赖性控制产生了一种简单而稳定的染色体汇聚自组织机制。