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富含核的蛋白磷酸酶 4 确保核溶解前外动粒的组装。

Nuclear-enriched protein phosphatase 4 ensures outer kinetochore assembly prior to nuclear dissolution.

机构信息

Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto, Portugal.

Instituto de Biologia Molecular e Celular - IBMC, Universidade do Porto , Porto, Portugal.

出版信息

J Cell Biol. 2023 Mar 6;222(3). doi: 10.1083/jcb.202208154. Epub 2023 Jan 31.

DOI:10.1083/jcb.202208154
PMID:36719399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9930252/
Abstract

A landmark event in the transition from interphase to mitosis in metazoans is nuclear envelope breakdown (NEBD). Important mitotic events occur prior to NEBD, including condensation of replicated chromosomes and assembly of kinetochores to rapidly engage spindle microtubules. Here, we show that nuclear-enriched protein phosphatase 4 (PP4) ensures robust assembly of the microtubule-coupling outer kinetochore prior to NEBD. In the absence of PP4, chromosomes exhibit extended monopolar orientation after NEBD and subsequently mis-segregate. A secondary consequence of diminished outer kinetochore assembly is defective sister chromatid resolution. After NEBD, a cytoplasmic activity compensates for PP4 loss, leading to outer kinetochore assembly and recovery of chromosomes from monopolar orientation to significant bi-orientation. The Ndc80-Ska microtubule-binding module of the outer kinetochore is required for this recovery. PP4 associates with the inner kinetochore protein CENP-C; however, disrupting the PP4-CENP-C interaction does not perturb chromosome segregation. These results establish that PP4-dependent outer kinetochore assembly prior to NEBD is critical for timely and proper engagement of chromosomes with spindle microtubules.

摘要

在后生动物从间期中向有丝分裂的转变过程中，核膜破裂（nuclear envelope breakdown，NEBD）是一个重要的里程碑事件。在 NEBD 之前，会发生许多重要的有丝分裂事件，包括复制染色体的浓缩和动粒向纺锤体微管的快速组装。在这里，我们发现富含核的蛋白磷酸酶 4（protein phosphatase 4，PP4）确保了微管连接的外动粒在 NEBD 之前的稳健组装。在没有 PP4 的情况下，染色体在 NEBD 后表现出延伸的单极取向，随后发生错误分离。外动粒组装减少的次要后果是姐妹染色单体的分离缺陷。在 NEBD 之后，细胞质中的一种活性物质可以弥补 PP4 的缺失，从而导致外动粒的组装，并使染色体从单极取向恢复到显著的双极取向。外动粒的 Ndc80-Ska 微管结合模块是恢复所必需的。PP4 与内动粒蛋白 CENP-C 相关联；然而，破坏 PP4-CENP-C 相互作用并不会干扰染色体分离。这些结果表明，NEBD 之前依赖于 PP4 的外动粒组装对于染色体与纺锤体微管的及时和正确结合至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/36308fb21bd0/JCB_202208154_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/a3dc92b4e4e5/JCB_202208154_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/a2da37db064e/JCB_202208154_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/470a3307ca2d/JCB_202208154_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/517ebe35aed1/JCB_202208154_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/506d1898a944/JCB_202208154_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/48c5dbc4ceac/JCB_202208154_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/af3cfd6c0dd1/JCB_202208154_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/36308fb21bd0/JCB_202208154_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/a3dc92b4e4e5/JCB_202208154_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/a2da37db064e/JCB_202208154_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/470a3307ca2d/JCB_202208154_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/517ebe35aed1/JCB_202208154_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/506d1898a944/JCB_202208154_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/48c5dbc4ceac/JCB_202208154_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/af3cfd6c0dd1/JCB_202208154_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5e/9930252/36308fb21bd0/JCB_202208154_Fig5.jpg

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Mitotic chromosomes.有丝分裂染色体。
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