Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, Edinburgh, United Kingdom.
Elife. 2024 Apr 2;13:RP93522. doi: 10.7554/eLife.93522.
The chromosomal passenger complex (CPC) is an important regulator of cell division, which shows dynamic subcellular localization throughout mitosis, including kinetochores and the spindle midzone. In traditional model eukaryotes such as yeasts and humans, the CPC consists of the catalytic subunit Aurora B kinase, its activator INCENP, and the localization module proteins Borealin and Survivin. Intriguingly, Aurora B and INCENP as well as their localization pattern are conserved in kinetoplastids, an evolutionarily divergent group of eukaryotes that possess unique kinetochore proteins and lack homologs of Borealin or Survivin. It is not understood how the kinetoplastid CPC assembles nor how it is targeted to its subcellular destinations during the cell cycle. Here, we identify two orphan kinesins, KIN-A and KIN-B, as bona fide CPC proteins in , the kinetoplastid parasite that causes African sleeping sickness. KIN-A and KIN-B form a scaffold for the assembly of the remaining CPC subunits. We show that the C-terminal unstructured tail of KIN-A interacts with the KKT8 complex at kinetochores, while its N-terminal motor domain promotes CPC translocation to spindle microtubules. Thus, the KIN-A:KIN-B complex constitutes a unique 'two-in-one' CPC localization module, which directs the CPC to kinetochores from S phase until metaphase and to the central spindle in anaphase. Our findings highlight the evolutionary diversity of CPC proteins and raise the possibility that kinesins may have served as the original transport vehicles for Aurora kinases in early eukaryotes.
染色体乘客复合物（CPC）是细胞分裂的重要调节剂，在有丝分裂过程中表现出动态的亚细胞定位，包括动粒和纺锤体中间区。在传统的模式真核生物如酵母和人类中，CPC 由催化亚基 Aurora B 激酶、其激活剂 INCENP 以及定位模块蛋白 Borealin 和 Survivin 组成。有趣的是，Aurora B 和 INCENP 及其定位模式在动基体生物中是保守的，动基体生物是一组进化上不同的真核生物，它们具有独特的动粒蛋白，缺乏 Borealin 或 Survivin 的同源物。目前尚不清楚动基体生物的 CPC 是如何组装的，也不清楚它在细胞周期中是如何被靶向到其亚细胞目的地的。在这里，我们鉴定了两种孤儿驱动蛋白 KIN-A 和 KIN-B，它们是引起非洲昏睡病的动基体寄生虫 中的 CPC 蛋白。KIN-A 和 KIN-B 形成了剩余 CPC 亚基组装的支架。我们表明，KIN-A 的 C 端无结构尾部与动粒处的 KKT8 复合物相互作用，而其 N 端运动结构域则促进 CPC 向纺锤体微管的易位。因此，KIN-A:KIN-B 复合物构成了一个独特的“一体两用”CPC 定位模块，它将 CPC 从 S 期引导到中期的动粒，并在后期引导到中心纺锤体。我们的发现突出了 CPC 蛋白的进化多样性，并提出了这样一种可能性，即驱动蛋白可能在早期真核生物中充当 Aurora 激酶的原始运输载体。
