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自噬介导的中间体环降解是胞质分裂后的一个事件。

Midbody ring disposal by autophagy is a post-abscission event of cytokinesis.

作者信息

Pohl Christian, Jentsch Stefan

机构信息

Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

出版信息

Nat Cell Biol. 2009 Jan;11(1):65-70. doi: 10.1038/ncb1813. Epub 2008 Dec 14.

DOI:10.1038/ncb1813
PMID:19079246
Abstract

At the end of cytokinesis, the dividing cells are connected by an intercellular bridge, containing the midbody along with a single, densely ubiquitylated, circular structure called the midbody ring (MR). Recent studies revealed that the MR serves as a target site for membrane delivery and as a physical barrier between the prospective daughter cells. The MR materializes in telophase, localizes to the intercellular bridge during cytokinesis, and moves asymmetrically into one cell after abscission. Daughter cells rarely accumulate MRs of previous divisions, but how these large structures finally disappear remains unknown. Here, we show that MRs are discarded by autophagy, which involves their sequestration into autophagosomes and delivery to lysosomes for degradation. Notably, autophagy factors, such as the ubiquitin adaptor p62 (Refs 4, 5) and the ubiquitin-related protein Atg8 (ref. 6), associate with the MR during abscission, suggesting that autophagy is coupled to cytokinesis. Moreover, MRs accumulate in cells of patients with lysosomal storage disorders, indicating that defective MR disposal is characteristic of these diseases. Thus our findings suggest that autophagy has a broader role than previously assumed, and that cell renovation by clearing from superfluous large macromolecular assemblies, such as MRs, is an important autophagic function.

摘要

在胞质分裂结束时,正在分裂的细胞通过一个细胞间桥相连,该桥包含中体以及一个单一的、高度泛素化的环状结构,称为中体环(MR)。最近的研究表明,MR作为膜递送的靶位点以及未来子细胞之间的物理屏障。MR在末期形成,在胞质分裂期间定位于细胞间桥,并在脱离后不对称地进入一个细胞。子细胞很少积累先前分裂产生的MR,但这些大结构最终如何消失仍不清楚。在这里,我们表明MR通过自噬被清除,这涉及它们被隔离到自噬体中并输送到溶酶体进行降解。值得注意的是,自噬因子,如泛素衔接蛋白p62(参考文献4、5)和泛素相关蛋白Atg8(参考文献6),在脱离过程中与MR相关联,表明自噬与胞质分裂相关。此外,MR在溶酶体贮积症患者的细胞中积累,表明MR处理缺陷是这些疾病的特征。因此,我们的研究结果表明自噬的作用比以前认为的更广泛,并且通过清除多余的大分子组装体(如MR)进行细胞更新是一种重要的自噬功能。

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本文引用的文献

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Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis.胞质分裂过程中中央纺锤体上泛素化和去泛素化的动态调控。
J Cell Sci. 2008 Apr 15;121(Pt 8):1325-33. doi: 10.1242/jcs.027417.
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Final stages of cytokinesis and midbody ring formation are controlled by BRUCE.胞质分裂的最后阶段和中间体环的形成由BRUCE控制。
Cell. 2008 Mar 7;132(5):832-45. doi: 10.1016/j.cell.2008.01.012.
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Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome.
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Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness.溶酶体在细胞代谢、细胞周期和干性的交汇点。
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They Might Cut It-Lysosomes and Autophagy in Mitotic Progression.它们可能会切断它——有丝分裂进程中的溶酶体与自噬
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Inhibition of selective autophagy by members of the herpesvirus ubiquitin-deconjugase family.疱疹病毒泛素去连接酶家族成员抑制选择性自噬。
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通过巨自噬和蛋白酶体对错误折叠蛋白降解途径进行分类、识别和激活。
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A block of autophagy in lysosomal storage disorders.溶酶体贮积症中的自噬阻断。
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Cell cycle-dependent induction of autophagy, mitophagy and reticulophagy.细胞周期依赖性自噬、线粒体自噬和内质网自噬的诱导
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Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis.自噬减轻乳腺肿瘤发生过程中的代谢应激和基因组损伤。
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p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.p62/SQSTM1直接与Atg8/LC3结合,以促进自噬对泛素化蛋白聚集体的降解。
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