Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Translational Research Centre in Onco-haematology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
J Cell Sci. 2022 Apr 15;135(8). doi: 10.1242/jcs.259120. Epub 2022 Apr 21.
Centrioles are central structural elements of centrosomes and cilia. In human cells, daughter centrioles are assembled adjacent to existing centrioles in S-phase and reach their full functionality with the formation of distal and subdistal appendages one-and-a-half cell cycles later, as they exit their second mitosis. Current models postulate that the centriolar protein centrobin acts as placeholder for distal appendage proteins that must be removed to complete distal appendage formation. Here, we investigated, in non-transformed human epithelial RPE1 cells, the mechanisms controlling centrobin removal and its effect on distal appendage formation. Our data are consistent with a speculative model in which centrobin is removed from older centrioles due to a higher affinity for the newly born daughter centrioles, under the control of the centrosomal kinase PLK1. This removal also depends on the presence of subdistal appendage proteins on the oldest centriole. Removing centrobin, however, is not required for the recruitment of distal appendage proteins, even though this process is equally dependent on PLK1. We conclude that PLK1 kinase regulates centrobin removal and distal appendage formation during centriole maturation via separate pathways.
中心体是中心体和纤毛的核心结构元件。在人类细胞中，子中心体在 S 期组装在现有中心体的旁边，并且在它们退出第二次有丝分裂后的一个半细胞周期后，通过形成远端和亚远端附属物而达到其完整的功能。当前的模型假设中心体蛋白 centribin 充当远端附属物蛋白的占位符，这些蛋白必须被移除以完成远端附属物的形成。在这里，我们在非转化的人上皮 RPE1 细胞中研究了控制 centribin 去除及其对远端附属物形成的影响的机制。我们的数据与一个推测模型一致，即由于新生成的子中心体具有更高的亲和力，centribin 从较旧的中心体中被去除，这受中心体激酶 PLK1 的控制。这种去除还取决于最古老的中心体上是否存在亚远端附属物蛋白。然而，即使这个过程同样依赖于 PLK1，去除 centribin 对于招募远端附属物蛋白也不是必需的。我们得出结论，PLK1 激酶通过独立的途径调节中心体成熟过程中的 centribin 去除和远端附属物的形成。
