Molecular, Cellular and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
J Cell Sci. 2024 Nov 15;137(22). doi: 10.1242/jcs.262327. Epub 2024 Nov 28.
Polo-like kinase 1 (PLK-1) is present in centrosomes, the nuclear envelope and kinetochores and plays a significant role in meiosis and mitosis. PLK-1 depletion or inhibition has severe consequences for spindle assembly, spindle assembly checkpoint (SAC) activation, chromosome segregation and cytokinesis. BUB-1 targets PLK-1 to the outer kinetochore and, in mammals, the inner kinetochore PLK1 targeting is mediated by the constitutive centromere associated network (CCAN). BUB-1-targeted PLK-1 plays a key role in SAC activation and has a SAC-independent role through targeting CDC-20. In contrast, whether there is a specific, non-redundant role for inner kinetochore targeted PLK-1 is unknown. Here, we used the Caenorhabditis elegans embryo to study the role of inner kinetochore PLK-1. We found that CENP-C, the sole CCAN component in C. elegans and other species, targets PLK-1 to the inner kinetochore during prometaphase and metaphase. Disruption of the CENP-C-PLK-1 interaction leads to an imbalance in kinetochore components and a defect in chromosome congression, without affecting CDC-20 recruitment. These findings indicate that PLK-1 kinetochore recruitment by CENP-C has at least partially distinct functions from outer kinetochore PLK-1, providing a platform for a better understanding of the different roles played by PLK-1 during mitosis.
丝氨酸/苏氨酸激酶 1(PLK-1)存在于中心体、核膜和动粒中,在减数分裂和有丝分裂中发挥重要作用。PLK-1 的耗竭或抑制会对纺锤体组装、纺锤体组装检查点(SAC)的激活、染色体分离和胞质分裂产生严重影响。BUB-1 将 PLK-1 靶向到外动粒,而在哺乳动物中,内动粒 PLK1 靶向由组成型着丝粒相关网络(CCAN)介导。BUB-1 靶向的 PLK-1 在 SAC 激活中起关键作用,并通过靶向 CDC-20 发挥 SAC 独立作用。相比之下,内动粒靶向的 PLK-1 是否具有特定的、非冗余作用尚不清楚。在这里,我们使用秀丽隐杆线虫胚胎来研究内动粒 PLK-1 的作用。我们发现,CENP-C 是秀丽隐杆线虫和其他物种中唯一的 CCAN 成分,在前期和中期将 PLK-1 靶向到内动粒。破坏 CENP-C-PLK-1 相互作用会导致动粒成分失衡和染色体向心性运动缺陷,而不影响 CDC-20 的募集。这些发现表明,CENP-C 对 PLK-1 动粒的募集至少具有与外动粒 PLK-1 不同的功能,为更好地理解 PLK-1 在有丝分裂过程中发挥的不同作用提供了一个平台。