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中心体 PP2A 调控纺锤体和着丝粒相关(Ska)复合物的着丝粒募集

Kinetochore Recruitment of the Spindle and Kinetochore-Associated (Ska) Complex Is Regulated by Centrosomal PP2A in .

机构信息

Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.

Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada

出版信息

Genetics. 2019 Jun;212(2):509-522. doi: 10.1534/genetics.119.302105. Epub 2019 Apr 24.

Abstract

During mitosis, kinetochore-microtubule interactions ensure that chromosomes are accurately segregated to daughter cells. RSA-1 (regulator of spindle assembly-1) is a regulatory B″ subunit of protein phosphatase 2A that was previously proposed to modulate microtubule dynamics during spindle assembly. We have identified a genetic interaction between the centrosomal protein, RSA-1, and the spindle- and kinetochore-associated (Ska) complex in In a forward genetic screen for suppressors of embryonic lethality, we identified mutations in and Loss of SKA-1 and SKA-3, as well as components of the KMN (KNL-1/MIS-12/NDC-80) complex and the microtubule end-binding protein EBP-2, all suppressed the embryonic lethality of These suppressors also disrupted the intracellular localization of the Ska complex, revealing a network of proteins that influence Ska function during mitosis. In embryos, SKA-1 is excessively and prematurely recruited to kinetochores during spindle assembly, but SKA-1 levels return to normal just prior to anaphase onset. Loss of the TPX2 homolog, TPXL-1, also resulted in overrecruitment of SKA-1 to the kinetochores and this correlated with the loss of Aurora A kinase on the spindle microtubules. We propose that regulates the kinetochore localization of the Ska complex, with spindle-associated Aurora A acting as a potential mediator. These data reveal a novel mechanism of protein phosphatase 2A function during mitosis involving a centrosome-based regulatory mechanism for Ska complex recruitment to the kinetochore.

摘要

在有丝分裂过程中,动粒微管相互作用确保染色体准确地分配到子细胞中。RSA-1(纺锤体组装调节因子-1)是蛋白磷酸酶 2A 的调节 B″亚基,先前被提议调节纺锤体组装过程中的微管动力学。我们已经确定了中心体蛋白 RSA-1 与纺锤体和动粒相关(Ska)复合物之间的遗传相互作用,在胚胎致死性的正向遗传筛选中,我们在 和 中发现了突变。SKA-1 和 SKA-3 的缺失,以及 KMN(KNL-1/MIS-12/NDC-80)复合物和微管末端结合蛋白 EBP-2 的成分,都抑制了 的胚胎致死性。这些抑制剂也破坏了 Ska 复合物的细胞内定位,揭示了影响 Ska 在有丝分裂过程中功能的蛋白质网络。在 胚胎中,SKA-1 在纺锤体组装过程中过早地被过度募集到动粒上,但在后期开始之前,SKA-1 水平恢复正常。TPX2 同源物 TPXL-1 的缺失也导致 SKA-1 过度募集到动粒上,这与纺锤体微管上 Aurora A 激酶的丢失相关。我们提出, 调节 Ska 复合物在动粒上的定位,纺锤体相关的 Aurora A 作为潜在的介导物起作用。这些数据揭示了蛋白磷酸酶 2A 在有丝分裂过程中功能的一种新机制,涉及到中心体为基础的 Ska 复合物募集到动粒的调节机制。

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本文引用的文献

1
Ectopic Activation of the Spindle Assembly Checkpoint Signaling Cascade Reveals Its Biochemical Design.
Curr Biol. 2019 Jan 7;29(1):104-119.e10. doi: 10.1016/j.cub.2018.11.054. Epub 2018 Dec 27.
2
Spindle assembly checkpoint strength is linked to cell fate in the Caenorhabditis elegans embryo.
Mol Biol Cell. 2018 Jun 15;29(12):1435-1448. doi: 10.1091/mbc.E18-04-0215. Epub 2018 Apr 24.
4
Two populations of cytoplasmic dynein contribute to spindle positioning in embryos.
J Cell Biol. 2017 Sep 4;216(9):2777-2793. doi: 10.1083/jcb.201607038. Epub 2017 Jul 24.
5
PP2A-B56γ is required for an efficient spindle assembly checkpoint.
Cell Cycle. 2017 Jun 18;16(12):1210-1219. doi: 10.1080/15384101.2017.1325042. Epub 2017 May 31.
6
Mechanism of Ska Recruitment by Ndc80 Complexes to Kinetochores.
Dev Cell. 2017 May 22;41(4):438-449.e4. doi: 10.1016/j.devcel.2017.04.020.
7
Dephosphorylation of the Ndc80 Tail Stabilizes Kinetochore-Microtubule Attachments via the Ska Complex.
Dev Cell. 2017 May 22;41(4):424-437.e4. doi: 10.1016/j.devcel.2017.04.013.
8
Congressing kinetochores progressively load Ska complexes to prevent force-dependent detachment.
J Cell Biol. 2017 Jun 5;216(6):1623-1639. doi: 10.1083/jcb.201607096. Epub 2017 May 11.
9
Protein Phosphatase 2A (PP2A) Regulates EG5 to Control Mitotic Progression.
Sci Rep. 2017 May 9;7(1):1630. doi: 10.1038/s41598-017-01915-w.
10
Ska3 Phosphorylated by Cdk1 Binds Ndc80 and Recruits Ska to Kinetochores to Promote Mitotic Progression.
Curr Biol. 2017 May 22;27(10):1477-1484.e4. doi: 10.1016/j.cub.2017.03.060. Epub 2017 May 4.

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