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PLK-1 靶向 CENP-C 调控秀丽隐杆线虫胚胎中的动粒功能。

CENP-C-targeted PLK-1 regulates kinetochore function in C. elegans embryos.

机构信息

Molecular, Cellular and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

出版信息

J Cell Sci. 2024 Nov 15;137(22). doi: 10.1242/jcs.262327. Epub 2024 Nov 28.

DOI:10.1242/jcs.262327
PMID:39355896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11634037/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/8fe8be380ca0/joces-137-262327-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/bfdefd4333fd/joces-137-262327-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/658a523ac918/joces-137-262327-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/24d3e30ce588/joces-137-262327-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/8fe8be380ca0/joces-137-262327-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/bfdefd4333fd/joces-137-262327-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/658a523ac918/joces-137-262327-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/24d3e30ce588/joces-137-262327-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c85/11634037/8fe8be380ca0/joces-137-262327-g4.jpg

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本文引用的文献

1
BUB-1-bound PLK-1 directs CDC-20 kinetochore recruitment to ensure timely embryonic mitoses.BUB-1 结合的 PLK-1 指导 CDC-20 着丝粒招募以确保胚胎有丝分裂的及时性。
Curr Biol. 2023 Jun 5;33(11):2291-2299.e10. doi: 10.1016/j.cub.2023.04.021. Epub 2023 May 2.
2
BUB-1 and CENP-C recruit PLK-1 to control chromosome alignment and segregation during meiosis I in oocytes.BUB-1 和 CENP-C 招募 PLK-1 来控制卵母细胞减数分裂 I 中的染色体排列和分离。
Elife. 2023 Apr 17;12:e84057. doi: 10.7554/eLife.84057.
3
Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation.
Bub1 和 CENP-U 冗余地招募 Plk1 以稳定着丝粒-微管连接,确保染色体的准确分离。
Cell Rep. 2021 Sep 21;36(12):109740. doi: 10.1016/j.celrep.2021.109740.
4
BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I in oocytes.BUB-1 靶向 PP2A:B56 以调节卵母细胞减数分裂 I 中的染色体向心性聚集。
Elife. 2020 Dec 23;9:e65307. doi: 10.7554/eLife.65307.
5
BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis.在有丝分裂中,由 CDK1 引发的 BUB1 和 CENP-U 是 PLK1 动粒的主要受体。
Mol Cell. 2021 Jan 7;81(1):67-87.e9. doi: 10.1016/j.molcel.2020.10.040. Epub 2020 Nov 27.
6
Channel Nucleoporins Recruit PLK-1 to Nuclear Pore Complexes to Direct Nuclear Envelope Breakdown in C. elegans.通道核孔蛋白将PLK-1招募至核孔复合体以指导秀丽隐杆线虫的核膜破裂。
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