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驱动蛋白-7 家族成员 CENP-E 介导减数分裂 I 中染色体的排列和纺锤体组装检查点。

Kinesin-7 CENP-E mediates chromosome alignment and spindle assembly checkpoint in meiosis I.

机构信息

Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, Fujian, China.

Key Laboratory of Stem Cell Engineering and Regenerative Medicine, Fujian Province University, Fuzhou, 350122, Fujian, China.

出版信息

Chromosoma. 2024 Apr;133(2):149-168. doi: 10.1007/s00412-024-00818-w. Epub 2024 Mar 8.

DOI:10.1007/s00412-024-00818-w
PMID:38456964
Abstract

In eukaryotes, meiosis is the genetic basis for sexual reproduction, which is important for chromosome stability and species evolution. The defects in meiosis usually lead to chromosome aneuploidy, reduced gamete number, and genetic diseases, but the pathogenic mechanisms are not well clarified. Kinesin-7 CENP-E is a key regulator in chromosome alignment and spindle assembly checkpoint in cell division. However, the functions and mechanisms of CENP-E in male meiosis remain largely unknown. In this study, we have revealed that the CENP-E gene was highly expressed in the rat testis. CENP-E inhibition influences chromosome alignment and spindle organization in metaphase I spermatocytes. We have found that a portion of misaligned homologous chromosomes is located at the spindle poles after CENP-E inhibition, which further activates the spindle assembly checkpoint during the metaphase-to-anaphase transition in rat spermatocytes. Furthermore, CENP-E depletion leads to abnormal spermatogenesis, reduced sperm count, and abnormal sperm head structure. Our findings have elucidated that CENP-E is essential for homologous chromosome alignment and spindle assembly checkpoint in spermatocytes, which further contribute to chromosome stability and sperm cell quality during spermatogenesis.

摘要

在真核生物中,减数分裂是有性生殖的遗传基础,对于染色体稳定性和物种进化至关重要。减数分裂的缺陷通常导致染色体非整倍体、配子数量减少和遗传疾病,但发病机制尚不清楚。驱动蛋白-7 着丝粒蛋白-E(CENP-E)是细胞分裂中染色体排列和纺锤体组装检查点的关键调节剂。然而,CENP-E 在雄性减数分裂中的功能和机制在很大程度上仍不清楚。在这项研究中,我们揭示了 CENP-E 基因在大鼠睾丸中高度表达。CENP-E 抑制会影响中期 I 精母细胞中的染色体排列和纺锤体组织。我们发现,CENP-E 抑制后一部分未对齐的同源染色体位于纺锤体极,这进一步激活了大鼠精母细胞从中期到后期过渡过程中的纺锤体组装检查点。此外,CENP-E 耗竭会导致精子发生异常、精子数量减少和精子头部结构异常。我们的研究结果表明,CENP-E 对于精母细胞中的同源染色体排列和纺锤体组装检查点至关重要,这进一步有助于减数分裂过程中染色体稳定性和精子细胞质量。

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本文引用的文献

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Reproductive genomics of the mouse: implications for human fertility and infertility.小鼠生殖基因组学:对人类生育力和不育症的影响。
Development. 2023 Feb 15;150(4). doi: 10.1242/dev.201313. Epub 2023 Feb 13.
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Kinesin-7 CENP-E is essential for chromosome alignment and spindle assembly of mouse spermatocytes.驱动蛋白-7 中心体定位蛋白-E 对于小鼠精母细胞的染色体排列和纺锤体组装是必需的。
Biochim Biophys Acta Mol Cell Res. 2022 Sep;1869(9):119306. doi: 10.1016/j.bbamcr.2022.119306. Epub 2022 Jun 6.
3
Recurrent pregnancy loss: fewer chromosomal abnormalities in products of conception? a meta-analysis.
复发性流产:妊娠产物中染色体异常减少?一项荟萃分析。
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Microtubule-sliding modules based on kinesins EG5 and PRC1-dependent KIF4A drive human spindle elongation.基于驱动蛋白 EG5 和 PRC1 依赖性 KIF4A 的微管滑动模块驱动人纺锤体伸长。
Dev Cell. 2021 May 3;56(9):1253-1267.e10. doi: 10.1016/j.devcel.2021.04.005. Epub 2021 Apr 27.
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CENPE Inhibition Leads to Mitotic Catastrophe and DNA Damage in Medulloblastoma Cells.CENPE抑制导致髓母细胞瘤细胞发生有丝分裂灾难和DNA损伤。
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Kinesin-7 CENP-E regulates the formation and structural maintenance of the acrosome.驱动蛋白-7 中心体蛋白-E 调控顶体的形成和结构维持。
Cell Tissue Res. 2021 Mar;383(3):1167-1182. doi: 10.1007/s00441-020-03341-3. Epub 2020 Nov 25.
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The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment.BubR1 的 C 端螺旋对于 CENP-E 依赖性染色体排列至关重要。
J Cell Sci. 2020 Aug 25;133(16):jcs246025. doi: 10.1242/jcs.246025.
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Kinesin-7 CENP-E regulates chromosome alignment and genome stability of spermatogenic cells.驱动蛋白7 CENP-E调节生精细胞的染色体排列和基因组稳定性。
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Leaving no-one behind: how CENP-E facilitates chromosome alignment.一个都不能少:CENP-E 如何促进染色体排列。
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