Spatiotemporal Proteomic Analysis of Stress Granule Disassembly Using APEX Reveals Regulation by SUMOylation and Links to ALS Pathogenesis.
Spatiotemporal Proteomic Analysis of Stress Granule Disassembly Using APEX Reveals Regulation by SUMOylation and Links to ALS Pathogenesis.
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DOI：
10.1016/j.molcel.2020.10.032
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发表时间：
2020-12-03
期刊：
影响因子：
16
通讯作者：
Hornstein E
中科院分区：
文献类型：
--
作者：
Marmor-Kollet H;Siany A;Kedersha N;Knafo N;Rivkin N;Danino YM;Moens TG;Olender T;Sheban D;Cohen N;Dadosh T;Addadi Y;Ravid R;Eitan C;Toth Cohen B;Hofmann S;Riggs CL;Advani VM;Higginbottom A;Cooper-Knock J;Hanna JH;Merbl Y;Van Den Bosch L;Anderson P;Ivanov P;Geiger T;Hornstein E
应激颗粒（Stress granules，SG）是蛋白质和非翻译mRNA的细胞质集合体。虽然已经了解了很多关于SG的形成，一个主要的差距仍然是在了解组成的变化SG在正常拆卸和疾病条件下进行。在这里，我们解决这个差距的SG时间拆卸序列使用多诱饵APEX接近蛋白质组学的蛋白质组学解剖。我们发现了109种新的SG蛋白，并表征了不同的SG亚结构。我们揭示了几十个拆卸参与蛋白（DEP），其中一些发挥功能的SG拆卸，包括小泛素样修饰（SUMO）共轭酶的作用。我们进一步证明SUMO化调节SG分解和SG形成。肌萎缩侧索硬化症（ALS）相关的C9 ORF 72二肽的平行蛋白质组学发现，在SG拆卸和受损的SUMO化过程中，DEP募集减弱。因此，SUMO活性改善了果蝇中C9 ORF 72-ALS相关的神经变性。通过解剖SG时空蛋白质组景观，我们提供了一个深入的资源，为未来的工作SG功能，并揭示基本的和疾病相关的机制SG拆卸。Marmor-Kollet等人利用邻近蛋白质组学来鉴定健康和疾病中的应激颗粒组成、内部组织和调节性分解机制。包括SUMO结合酶在内的解聚参与蛋白（DEPs）对ALS样条件下正常应激颗粒的解聚和失调至关重要。
Stress granules (SGs) are cytoplasmic assemblies of proteins and non-translating mRNAs. Whereas much has been learned about SG formation, a major gap remains in understanding the compositional changes SGs undergo during normal disassembly and under disease conditions. Here, we address this gap by proteomic dissection of the SG temporal disassembly sequence using multi-bait APEX proximity proteomics. We discover 109 novel SG proteins and characterize distinct SG substructures. We reveal dozens of disassembly-engaged proteins (DEPs), some of which play functional roles in SG disassembly, including small ubiquitin-like modifier (SUMO) conjugating enzymes. We further demonstrate that SUMOylation regulates SG disassembly and SG formation. Parallel proteomics with amyotrophic lateral sclerosis (ALS)-associated C9ORF72 dipeptides uncovered attenuated DEP recruitment during SG disassembly and impaired SUMOylation. Accordingly, SUMO activity ameliorated C9ORF72-ALS-related neurodegeneration in Drosophila. By dissecting the SG spatiotemporal proteomic landscape, we provide an in-depth resource for future work on SG function and reveal basic and disease-relevant mechanisms of SG disassembly. Marmor-Kollet et al. utilize proximity proteomics to identify stress granule composition, internal organization, and mechanisms of regulated disassembly in health and disease. Disassembly-engaged proteins (DEPs), including SUMO-conjugating enzymes, are critical for normal stress granule disassembly and dysregulated in ALS-like conditions.
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影响因子：
16
作者：
Dao TP;Kolaitis RM;Kim HJ;O'Donovan K;Martyniak B;Colicino E;Hehnly H;Taylor JP;Castañeda CA
通讯作者：
Castañeda CA
影响因子：
4.4
作者：
Anders M;Chelysheva I;Goebel I;Trenkner T;Zhou J;Mao Y;Verzini S;Qian SB;Ignatova Z
通讯作者：
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DOI：
10.1083/jcb.201408092
发表时间：
2015-04-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Aulas A;Caron G;Gkogkas CG;Mohamed NV;Destroismaisons L;Sonenberg N;Leclerc N;Parker JA;Vande Velde C
通讯作者：
Vande Velde C
影响因子：
64.5
作者：
Feric M;Vaidya N;Harmon TS;Mitrea DM;Zhu L;Richardson TM;Kriwacki RW;Pappu RV;Brangwynne CP
通讯作者：
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影响因子：
4
作者：
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通讯作者：
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