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Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing

机译:Spastin和ESCRT-III协调有丝分裂纺锤体的拆卸和核包膜密封

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摘要

At the onset of metazoan cell division the nuclear envelope breaks down to enable capture of chromosomes by the microtubule-containing spindle apparatus(1). During anaphase, when chromosomes have separated, the nuclear envelope is reassembled around the forming daughter nuclei(1,2). How the nuclear envelope is sealed, and how this is coordinated with spindle disassembly, is largely unknown. Here we show that endosomal sorting complex required for transport (ESCRT)-III, previously found to promote membrane constriction and sealing during receptor sorting, virus budding, cytokinesis and plasma membrane repair(3-6), is transiently recruited to the reassembling nuclear envelope during late anaphase. ESCRT-III and its regulatory AAA (ATPase associated with diverse cellular activities) ATPase VPS4 are specifically recruited by the ESCRT-III-like protein CHMP7 to sites where the reforming nuclear envelope engulfs spindle microtubules. Subsequent association of another ESCRT-III-like protein, IST1, directly recruits the AAA ATPase spastin to sever microtubules. Disrupting spastin function impairs spindle disassembly and results in extended localization of ESCRT-III at the nuclear envelope. Interference with ESCRT-III functions in anaphase is accompanied by delayed microtubule disassembly, compromised nuclear integrity and the appearance of DNA damage foci in subsequent interphase. We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly at nuclear envelope-microtubule intersection sites during mitotic exit to ensure nuclear integrity and genome safeguarding, with a striking mechanistic parallel to cytokinetic abscission(7).
机译:在后生细胞分裂开始时,核被膜破裂,使含有微管的纺锤体能够捕获染色体(1)。在后期,当染色体分离时,核被膜在形成的子核周围重新组装(1,2)。如何密封核壳,以及如何与主轴拆卸配合,在很大程度上尚不清楚。在这里,我们显示转运(ESCRT)-III所需的内体分选复合物(先前被发现可促进受体分选,病毒出芽,胞质分裂和质膜修复过程中的膜收缩和封闭)(3-6)被暂时招募到重组核膜中。在后期后期。 ESCRT-III样蛋白CHMP7专门募集了ESCRT-III及其调节性AAA(与多种细胞活动相关的ATPase)ATPase VPS4到重整核被膜吞噬纺锤体微管的位点。随后的另一个类似ESCRT-III的蛋白IST1的关联,直接将AAA ATPase spastin募集到切断微管。破坏spastin功能会损害纺锤体的拆卸,并导致ESCRT-III在核膜上的定位延长。在后期干扰ESCRT-III的功能伴随着微管的拆卸延迟,核完整性受损以及随后的相间DNA损伤灶的出现。我们建议ESCRT-III,VPS4和spastin在有丝分裂退出期间协同协调核包膜的封闭和核包膜-微管相交部位的纺锤体拆卸,以确保核完整性和基因组保护,并具有与细胞动力学破坏平行的惊人机制(7)。

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  • 来源
    《Nature》 |2015年第7555期|231-235|共5页
  • 作者单位

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

    Norwegian Univ Sci & Technol, Fac Med, Ctr Mol Inflammat Res, N-7491 Trondheim, Norway|Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway|Univ Oslo, Fac Med, Ctr Canc Biomed, N-0379 Oslo, Norway;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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