• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

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。

Microtubule-sliding modules based on kinesins EG5 and PRC1-dependent KIF4A drive human spindle elongation.

机构信息

Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.

Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.

出版信息

Dev Cell. 2021 May 3;56(9):1253-1267.e10. doi: 10.1016/j.devcel.2021.04.005. Epub 2021 Apr 27.

DOI:10.1016/j.devcel.2021.04.005
PMID:33910056
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8098747/
Abstract

Proper chromosome segregation into two future daughter cells requires the mitotic spindle to elongate in anaphase. However, although some candidate proteins are implicated in this process, the molecular mechanism that drives spindle elongation in human cells is unknown. Using combined depletion and inactivation assays together with CRISPR technology to explore redundancy between multiple targets, we discovered that the force-generating mechanism of spindle elongation consists of EG5/kinesin-5 together with the PRC1-dependent motor KIF4A/kinesin-4, with contribution from kinesin-6 and kinesin-8. Disruption of EG5 and KIF4A leads to total failure of chromosome segregation due to blocked spindle elongation, despite poleward chromosome motion. Tubulin photoactivation, stimulated emission depletion (STED), and expansion microscopy show that perturbation of both proteins impairs midzone microtubule sliding without affecting microtubule stability. Thus, two mechanistically distinct sliding modules, one based on a self-sustained and the other on a crosslinker-assisted motor, power the mechanism that drives spindle elongation in human cells.

摘要

正确的染色体分离到两个未来的子细胞中需要有丝分裂纺锤体在后期拉长。然而，尽管一些候选蛋白与这个过程有关，但驱动人类细胞纺锤体伸长的分子机制尚不清楚。我们使用组合的耗尽和失活测定以及 CRISPR 技术来探索多个靶标之间的冗余性，发现纺锤体伸长的力产生机制由 EG5/驱动蛋白-5 与依赖 PRC1 的马达 KIF4A/驱动蛋白-4 组成，驱动蛋白-6 和驱动蛋白-8 也有贡献。尽管染色体向极运动，但 EG5 和 KIF4A 的破坏会导致纺锤体伸长受阻，导致染色体完全分离失败。微管光激活、受激发射损耗（STED）和扩展显微镜显示，两种蛋白的扰动会损害中间区微管的滑动，而不影响微管的稳定性。因此，两种机械上不同的滑动模块，一种基于自维持，另一种基于交联辅助马达，为驱动人类细胞纺锤体伸长的机制提供动力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/d86acdd24579/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/f2654c1ec404/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/69a2e33fc946/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/6e100dbcd8c4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/a0583e1390cb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/f2d3b0ba5f1a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/2e49cb5c3971/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/78309765cd21/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/d86acdd24579/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/f2654c1ec404/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/69a2e33fc946/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/6e100dbcd8c4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/a0583e1390cb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/f2d3b0ba5f1a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/2e49cb5c3971/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/78309765cd21/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ead9/8098747/d86acdd24579/gr7.jpg

相似文献

1
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.
2
Computational Studies Reveal How Passive Cross-Linkers Regulate Anaphase Spindle Elongation.计算研究揭示了被动交联剂如何调节后期纺锤体的伸长。
J Phys Chem B. 2024 Feb 8;128(5):1194-1204. doi: 10.1021/acs.jpcb.3c07655. Epub 2024 Jan 30.
3
Antiparallel microtubule bundling supports KIF15-driven mitotic spindle assembly.反平行微管束支持 KIF15 驱动的有丝分裂纺锤体组装。
Mol Biol Cell. 2024 Jun 1;35(6):ar84. doi: 10.1091/mbc.E24-01-0023. Epub 2024 Apr 10.
4
Phosphorylation controls spatial and temporal activities of motor-PRC1 complexes to complete mitosis.磷酸化控制着运动-PRC1 复合物的空间和时间活动，以完成有丝分裂。
EMBO J. 2023 Nov 2;42(21):e113647. doi: 10.15252/embj.2023113647. Epub 2023 Aug 18.
5
Two modes of PRC1-mediated mechanical resistance to kinesin-driven microtubule network disruption.两种 PRC1 介导的机械抗性模式可抵抗驱动微管网络解聚的动力蛋白。
Curr Biol. 2021 Jun 21;31(12):2495-2506.e4. doi: 10.1016/j.cub.2021.03.034. Epub 2021 Apr 12.
6
Kinesin-8 and Dis1/TOG collaborate to limit spindle elongation from prophase to anaphase A for proper chromosome segregation in fission yeast.驱动蛋白-8 和 Dis1/TOG 协同作用，限制有丝分裂前期到后期 A 的纺锤体伸长，以实现裂殖酵母中染色体的正确分离。
J Cell Sci. 2019 Sep 23;132(18):jcs232306. doi: 10.1242/jcs.232306.
7
Kinesin-6 Klp9 orchestrates spindle elongation by regulating microtubule sliding and growth.驱动蛋白-6 Klp9 通过调节微管滑动和生长来协调纺锤体的伸长。
Elife. 2021 Jun 3;10:e67489. doi: 10.7554/eLife.67489.
8
Redundant microtubule crosslinkers prevent meiotic spindle bending to ensure diploid offspring in C. elegans.冗余的微管交联蛋白防止减数分裂纺锤体弯曲，以确保线虫产生二倍体后代。
PLoS Genet. 2023 Dec 27;19(12):e1011090. doi: 10.1371/journal.pgen.1011090. eCollection 2023 Dec.
9
Patronin mediates a switch from kinesin-13-dependent poleward flux to anaphase B spindle elongation.伴侣蛋白介导了从依赖于驱动蛋白-13 的极向运输到后期 B 纺锤体伸长的转换。
J Cell Biol. 2013 Oct 14;203(1):35-46. doi: 10.1083/jcb.201306001. Epub 2013 Oct 7.
10
The microtubule cross-linker Feo controls the midzone stability, motor composition, and elongation of the anaphase B spindle in Drosophila embryos.微管交联蛋白Feo控制果蝇胚胎后期B纺锤体的中区稳定性、马达蛋白组成和伸长。
Mol Biol Cell. 2015 Apr 15;26(8):1452-62. doi: 10.1091/mbc.E14-12-1631. Epub 2015 Feb 18.

引用本文的文献

1
Mechanical force locally damages, remodels and stabilizes the lattice of spindle microtubules.机械力会对纺锤体微管晶格造成局部损伤、重塑并使其稳定。
bioRxiv. 2025 Jun 6:2025.06.05.657915. doi: 10.1101/2025.06.05.657915.
2
Insights into the E2F target genes in breast cancer: associations of pathway genes with prognosis and immune cell filtration based on in silico and ex vivo analyses.乳腺癌中E2F靶基因的见解：基于计算机模拟和体外分析的通路基因与预后及免疫细胞浸润的关联
Cancer Cell Int. 2025 Jun 6;25(1):203. doi: 10.1186/s12935-025-03839-2.
3
Meiotic divisions and round spermatid formation do not require centriole duplication in mice.

本文引用的文献

1
Anaphase B: Long-standing models meet new concepts.后期 B：长期存在的模型遇到新概念。
Semin Cell Dev Biol. 2021 Sep;117:127-139. doi: 10.1016/j.semcdb.2021.03.023. Epub 2021 Apr 10.
2
Optogenetic control of PRC1 reveals its role in chromosome alignment on the spindle by overlap length-dependent forces.光遗传学控制 PRC1 揭示了其通过重叠长度依赖的力在纺锤体上的染色体排列中的作用。
Elife. 2021 Jan 22;10:e61170. doi: 10.7554/eLife.61170.
3
Expansion microscopy of the mitotic spindle.有丝分裂纺锤体的扩展显微镜技术。
减数分裂和圆形精子细胞的形成在小鼠中不需要中心粒复制。
PLoS Genet. 2025 Apr 28;21(4):e1011698. doi: 10.1371/journal.pgen.1011698. eCollection 2025 Apr.
4
Chromatin-associated α-satellite RNA maintains chromosome stability by reestablishing SAF-A in the mitotic cell cycle.与染色质相关的α-卫星RNA通过在有丝分裂细胞周期中重新建立SAF-A来维持染色体稳定性。
Nucleic Acids Res. 2025 Apr 10;53(7). doi: 10.1093/nar/gkaf294.
5
Comprehensive RNA-seq analysis of benign prostatic hyperplasia (BPH) in rats exposed to testosterone and estradiol.对暴露于睾酮和雌二醇的大鼠良性前列腺增生（BPH）进行的综合RNA测序分析。
Sci Rep. 2025 Jan 22;15(1):2750. doi: 10.1038/s41598-025-87205-2.
6
Super-Resolution Imaging of Mitotic Spindle Microtubules Using STED Microscopy.使用 STED 显微镜对有丝分裂纺锤体微管进行超分辨率成像。
Methods Mol Biol. 2025;2872:3-19. doi: 10.1007/978-1-0716-4224-5_1.
7
Torques within and outside the human spindle balance twist at anaphase.纺锤体内部和外部的扭矩在后期平衡扭转。
J Cell Biol. 2024 Sep 2;223(9). doi: 10.1083/jcb.202312046. Epub 2024 Jun 13.
8
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin.脊椎动物有丝分裂着丝粒是由黏合蛋白稳定的功能二分体结构。
Cell. 2024 Jun 6;187(12):3006-3023.e26. doi: 10.1016/j.cell.2024.04.014. Epub 2024 May 13.
9
Non-canonical role for the BAF complex subunit DPF3 in mitosis and ciliogenesis.BAF 复合物亚基 DPF3 在有丝分裂和纤毛发生中的非规范作用。
J Cell Sci. 2024 May 1;137(9). doi: 10.1242/jcs.261744. Epub 2024 May 13.
10
Kinesin-7 CENP-E mediates chromosome alignment and spindle assembly checkpoint in meiosis I.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。
Chromosoma. 2024 Apr;133(2):149-168. doi: 10.1007/s00412-024-00818-w. Epub 2024 Mar 8.
Methods Cell Biol. 2021;161:247-274. doi: 10.1016/bs.mcb.2020.04.014. Epub 2020 May 30.
4
Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins.人细胞中的微管极向流是由四个驱动蛋白的协调作用驱动的。
EMBO J. 2020 Dec 1;39(23):e105432. doi: 10.15252/embj.2020105432. Epub 2020 Oct 19.
5
The Mitotic Crosslinking Protein PRC1 Acts Like a Mechanical Dashpot to Resist Microtubule Sliding.有丝分裂交联蛋白 PRC1 像机械阻尼器一样抵抗微管滑动。
Dev Cell. 2020 Aug 10;54(3):367-378.e5. doi: 10.1016/j.devcel.2020.06.017. Epub 2020 Jul 7.
6
MKLP2 Is a Motile Kinesin that Transports the Chromosomal Passenger Complex during Anaphase.MKLP2 是一种运动驱动蛋白，在有丝分裂后期运输染色体乘客复合物。
Curr Biol. 2020 Jul 6;30(13):2628-2637.e9. doi: 10.1016/j.cub.2020.04.081. Epub 2020 Jun 4.
7
Small molecule allosteric uncoupling of microtubule depolymerase activity from motility in human Kinesin-5 during mitotic spindle assembly.小分子变构解偶联微管解聚酶活性与人类有丝分裂纺锤体组装过程中动力蛋白 Kinesin-5 的运动。
Sci Rep. 2019 Dec 27;9(1):19900. doi: 10.1038/s41598-019-56173-9.
8
Force-generating mechanisms of anaphase in human cells.有丝分裂后期人类细胞的力生成机制。
J Cell Sci. 2019 Sep 16;132(18):jcs231985. doi: 10.1242/jcs.231985.
9
Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk.通过 Aurora B-Cdk1 相互作用对后期有丝分裂退出进行时空调控。
Elife. 2019 Aug 19;8:e47646. doi: 10.7554/eLife.47646.
10
Central-spindle microtubules are strongly coupled to chromosomes during both anaphase A and anaphase B.有丝分裂后期 A 和有丝分裂后期 B 期间，中心纺锤体微管与染色体紧密结合。
Mol Biol Cell. 2019 Sep 1;30(19):2503-2514. doi: 10.1091/mbc.E19-01-0074. Epub 2019 Jul 24.