Cell Division and Cytoskeleton, Danish Cancer Society Research Center (DCRC), Strandboulevarden 49, 2100 Copenhagen, Denmark; Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Cell Division and Cytoskeleton, Danish Cancer Society Research Center (DCRC), Strandboulevarden 49, 2100 Copenhagen, Denmark.
Semin Cell Dev Biol. 2021 Sep;117:99-117. doi: 10.1016/j.semcdb.2021.05.016. Epub 2021 May 28.
The mitotic spindle is a bipolar cellular structure, built from tubulin polymers, called microtubules, and interacting proteins. This macromolecular machine orchestrates chromosome segregation, thereby ensuring accurate distribution of genetic material into the two daughter cells during cell division. Powered by GTP hydrolysis upon tubulin polymerization, the microtubule ends exhibit a metastable behavior known as the dynamic instability, during which they stochastically switch between the growth and shrinkage phases. In the context of the mitotic spindle, dynamic instability is furthermore regulated by microtubule-associated proteins and motor proteins, which enables the spindle to undergo profound changes during mitosis. This highly dynamic behavior is essential for chromosome capture and congression in prometaphase, as well as for chromosome alignment to the spindle equator in metaphase and their segregation in anaphase. In this review we focus on the mechanisms underlying microtubule dynamics and sliding and their importance for the maintenance of shape, structure and dynamics of the metaphase spindle. We discuss how these spindle properties are related to the phenomenon of microtubule poleward flux, highlighting its highly cooperative molecular basis and role in keeping the metaphase spindle at a steady state.
有丝分裂纺锤体是一种由微管蛋白（称为微管）和相互作用的蛋白质组成的双极细胞结构。这种大分子机器协调染色体分离，从而确保在细胞分裂过程中遗传物质准确地分配到两个子细胞中。在微管聚合时通过 GTP 水解提供动力，微管末端表现出一种称为动态不稳定性的亚稳态行为，在此期间它们随机在生长和收缩相之间切换。在有丝分裂纺锤体的背景下，微管相关蛋白和马达蛋白进一步调节动态不稳定性，使纺锤体在有丝分裂过程中发生深刻变化。这种高度动态的行为对于前期染色体的捕获和聚集以及中期染色体到纺锤体赤道面的对准和后期的分离至关重要。在这篇综述中，我们重点讨论了微管动力学和滑动的机制及其对中期纺锤体形状、结构和动力学的维持的重要性。我们讨论了这些纺锤体特性与微管极向流现象的关系，强调了其高度合作的分子基础及其在维持中期纺锤体处于稳定状态中的作用。
