The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles.
The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles.
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DOI：
10.1016/j.bbamcr.2021.119161
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发表时间：
2022-01
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影响因子：
--
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--
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无膜细胞器在真核细胞的进化过程中出现，作为细胞内结构域，其中多种蛋白质组织成复杂的结构以执行专门的功能，而不需要脂质双层隔室。在这里，我们描述了真核细胞的核周空间作为一个高度组织化的细胞骨架丝，有利于生物分子凝聚物的组装网络。使用生物信息学分析，我们表明，核周蛋白质组是丰富的内在障碍与几个蛋白质预测进行液-液相分离。我们还分析了免疫荧光和透射电子显微镜图像，显示细胞核和其他细胞器，如线粒体和溶酶体，或细胞核周区域内的特定蛋白质的标记之间的关联。总之，我们的数据支持存在一个核周致密的亚微米区域形成了一个组织良好的三维网络的结构和信号蛋白，包括几个蛋白质含有固有的无序区域与相行为。这种丝状细胞骨架蛋白的网络从细胞核延伸几微米，有助于局部拥挤，并组织核周空间内分子复合物的运动。我们的研究结果朝着理解真核细胞内的无膜区域如何作为生物分子凝聚物组装的枢纽，特别是核周空间迈出了关键一步。最后，对核周蛋白的疾病背景的评估显示，其表达的改变可导致几种病理状况，并且神经系统疾病和癌症是最常见的。
Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step towards understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent.
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影响因子：
4.6
作者：
Klus P;Cirillo D;Botta Orfila T;Gaetano Tartaglia G
通讯作者：
Gaetano Tartaglia G
影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
DOI：
10.1590/s0100-879x2004001200007
发表时间：
2004-12-01
影响因子：
2.3
作者：
Costa, M.L.;Escaleira, R.;Mermelstein, C.S.
通讯作者：
Mermelstein, C.S.
影响因子：
16
作者：
Kostylev MA;Tuttle MD;Lee S;Klein LE;Takahashi H;Cox TO;Gunther EC;Zilm KW;Strittmatter SM
通讯作者：
Strittmatter SM
影响因子：
19
作者：
Boeynaems S;Alberti S;Fawzi NL;Mittag T;Polymenidou M;Rousseau F;Schymkowitz J;Shorter J;Wolozin B;Van Den Bosch L;Tompa P;Fuxreiter M
通讯作者：
Fuxreiter M