FUS 的相分离被其核输入受体和精氨酸甲基化抑制。,Cell

当前位置： X-MOL 学术 › Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

FUS 的相分离被其核输入受体和精氨酸甲基化抑制。
Cell ( IF 45.5 ) Pub Date : 2018-Apr-19 , DOI: 10.1016/j.cell.2018.03.004
Mario Hofweber ₁ , Saskia Hutten ₂ , Benjamin Bourgeois ₃ , Emil Spreitzer ₃ , Annika Niedner-Boblenz ₄ , Martina Schifferer ₅ , Marc-David Ruepp ₆ , Mikael Simons ₅ , Dierk Niessing ₇ , Tobias Madl ₃ , Dorothee Dormann ₈

Affiliation

Biomedical Center (BMC), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany; Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany.
Biomedical Center (BMC), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany.
Institute of Molecular Biology & Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
Biomedical Center (BMC), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany; Institute of Structural Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85763 Neuherberg, Germany.
Institute of Neuronal Cell Biology, Technical University of Munich, 80805 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy); 81377 Munich, Germany.
Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland.
Biomedical Center (BMC), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany; Institute of Structural Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85763 Neuherberg, Germany; Institute of Pharmaceutical Biotechnology, Ulm University, 89081 Ulm, Germany.
Biomedical Center (BMC), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany; Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany; Munich Cluster for Systems Neurology (SyNergy); 81377 Munich, Germany.

细胞质 FUS 聚集体是额颞叶痴呆 (FTD) 或肌萎缩侧索硬化症 (ALS) 患者子集的病理标志。在这些患者中被破坏的一个关键步骤是由输入受体转运蛋白/核转运蛋白-β2 介导的 FUS 的核输入。在 ALS-FUS 患者中，这是由 FUS 的核定位信号 (NLS) 突变导致转运蛋白结合减弱。在 FTD-FUS 患者中，转运蛋白聚集，调节 FUS-转运蛋白相互作用的翻译后精氨酸甲基化丢失。在这里，我们表明转运蛋白和精氨酸甲基化具有超越核输入的关键功能，即抑制 RGG/RG 驱动的相分离和 FUS 的应力颗粒结合。ALS 相关的 FUS-NLS 突变削弱了转运蛋白的伴侣活性和 FUS 精氨酸甲基化的丧失，如 FTD-FUS 中所见，促进 FUS 的相分离和应力颗粒分配。我们的研究结果揭示了在 FUS 相关的神经变性中被破坏的两种液相稳态调节机制。

"点击查看英文标题和摘要"

更新日期：2018-04-26

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南