Cytoplasmic TDP-43 is involved in cell fate during stress recovery.
Cytoplasmic TDP-43 is involved in cell fate during stress recovery.
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DOI：
10.1093/hmg/ddab227
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发表时间：
2021-12-27
影响因子：
3.5
通讯作者：
Shaw CE
中科院分区：
文献类型：
--
作者：
Lee YB;Scotter EL;Lee DY;Troakes C;Mitchell J;Rogelj B;Gallo JM;Shaw CE
交互反应DNA结合蛋白43 （TDP-43）是一种RNA加工蛋白，对肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）的发病机制至关重要。核TDP-43在患者中错定位到细胞质，在那里它在受影响的神经元和胶质细胞中形成泛素阳性包体。生理上，胞质TDP-43与应激颗粒（SGs）有关。在这里，我们探讨了渗透和氧化应激后TDP-43的细胞质积累和应激颗粒的形成。我们发现山梨醇驱动TDP-43重新分布到细胞质中，而亚砷酸盐诱导细胞质中TDP-43向TIA-1阳性SGs募集。我们证明，通过渗透休克诱导TDP-43细胞质重新定位后的急性氧化应激可诱导聚（adp -核糖）聚合酶（PARP）裂解，从而引发细胞毒性。胞质TDP-43向多核糖体的募集发生在SH-SY5Y细胞应激模型中，并在FTD脑裂解液中观察到。此外，在应激恢复过程中，TDP-43颗粒中检测到加工体（p体）标记物DCP1a。总之，本研究支持细胞质TDP-43在控制应激细胞中蛋白质翻译中的核心作用。
Transactive response DNA binding protein 43 (TDP-43) is an RNA processing protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Nuclear TDP-43 mislocalizes in patients to the cytoplasm, where it forms ubiquitin-positive inclusions in affected neurons and glia. Physiologically, cytoplasmic TDP-43 is associated with stress granules (SGs). Here, we explored TDP-43 cytoplasmic accumulation and stress granule formation following osmotic and oxidative stress. We show that sorbitol drives TDP-43 redistribution to the cytoplasm, while arsenite induces the recruitment of cytoplasmic TDP-43 to TIA-1 positive SGs. We demonstrate that inducing acute oxidative stress after TDP-43 cytoplasmic relocalization by osmotic shock induces poly (ADP-ribose) polymerase (PARP) cleavage, which triggers cellular toxicity. Recruitment of cytoplasmic TDP-43 to polyribosomes occurs in an SH-SY5Y cellular stress model and is observed in FTD brain lysate. Moreover, the processing body (P-body) marker DCP1a is detected in TDP-43 granules during recovery from stress. Overall, this study supports a central role for cytoplasmic TDP-43 in controlling protein translation in stressed cells.
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影响因子：
3.7
作者：
Liu-Yesucevitz L;Bilgutay A;Zhang YJ;Vanderweyde T;Citro A;Mehta T;Zaarur N;McKee A;Bowser R;Sherman M;Petrucelli L;Wolozin B
通讯作者：
Wolozin B
影响因子：
4.8
作者：
Fontana F;Siva K;Denti MA
通讯作者：
Denti MA
影响因子：
9.9
作者：
Gliebus, G.;Bigio, E. H.;Geula, C.
通讯作者：
Geula, C.
DOI：
10.1016/s1474-4422(14)70219-4
发表时间：
2014-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Al-Chalabi A;Calvo A;Chio A;Colville S;Ellis CM;Hardiman O;Heverin M;Howard RS;Huisman MHB;Keren N;Leigh PN;Mazzini L;Mora G;Orrell RW;Rooney J;Scott KM;Scotton WJ;Seelen M;Shaw CE;Sidle KS;Swingler R;Tsuda M;Veldink JH;Visser AE;van den Berg LH;Pearce N
通讯作者：
Pearce N
DOI：
10.1016/s1877-1173(09)90004-7
发表时间：
2009
影响因子：
--
作者：
Kedersha N;Anderson P
通讯作者：
Anderson P