Reg1 and Snf1 regulate stress-induced relocalization of protein phosphatase-1 to cytoplasmic granules.
Reg1 and Snf1 regulate stress-induced relocalization of protein phosphatase-1 to cytoplasmic granules.
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DOI：
10.1111/febs.15802
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Hanna J
中科院分区：
文献类型：
--
作者：
Schnell HM;Jochem M;Micoogullari Y;Riggs CL;Ivanov P;Welsch H;Ravindran R;Anderson P;Robinson LC;Tatchell K;Hanna J
细胞功能的区隔化主要是通过膜结合细胞器的存在来实现的。然而，最近的研究提出了一种新的区隔化机制，这种机制由具有液滴样性质的无膜结构介导，并通过相分离产生。胞质应激颗粒（Cytoplasmic stress granules, SGs）是由亚砷酸盐、热休克和葡萄糖剥夺等多种应激源诱导形成的。目前的模型表明，SGs通过介导可逆翻译衰减在蛋白质稳态中起重要作用。蛋白磷酸酶-1 （PP1）是负责大多数丝氨酸/苏氨酸去磷酸化的中心细胞调节因子。在亚砷酸盐胁迫下，PP1的催化亚基Glc7重新定位到点状细胞质颗粒。这种定位的改变需要PP1最近描述的由多功能atp酶Cdc48和PP1的调控亚基Ypi1介导的成熟途径。Glc7的再定位是由其调控亚基Reg1及其靶标Snf1介导的，Snf1是amp依赖性蛋白激酶。令人惊讶的是，Glc7颗粒对亚砷酸盐具有高度特异性，与典型的SGs不同。亚砷酸盐诱导有效的翻译抑制和翻译恢复强烈依赖于Glc7，但独立于Glc7在调节eIF2α中的作用。这些结果提示了一种新的应激诱导细胞质颗粒形式和Glc7翻译控制的新模式。
The compartmentalization of cellular function is achieved largely through the existence of membrane-bound organelles. However, recent work suggests a novel mechanism of compartmentalization mediated by membraneless structures that have liquid droplet-like properties and arise through phase separation. Cytoplasmic stress granules (SGs) are the best characterized and are induced by various stressors including arsenite, heat shock, and glucose deprivation. Current models suggest that SGs play an important role in protein homeostasis by mediating reversible translation attenuation. Protein Phosphatase-1 (PP1) is a central cellular regulator responsible for most serine/threonine dephosphorylation. Here we show that upon arsenite stress, PP1’s catalytic subunit Glc7 relocalizes to punctate cytoplasmic granules. This altered localization requires PP1’s recently described maturation pathway mediated by the multifunctional ATPase Cdc48 and PP1’s regulatory subunit Ypi1. Glc7 relocalization is mediated by its regulatory subunit Reg1 and its target Snf1, the AMP-dependent protein kinase. Surprisingly, Glc7 granules are highly specific to arsenite and appear distinct from canonical SGs. Arsenite induces potent translational inhibition and translational recovery is strongly dependent on Glc7, but independent of Glc7’s well-established role in regulating eIF2α. These results suggest a novel form of stress-induced cytoplasmic granule and a new mode of translational control by Glc7.
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DOI：
10.15698/mic2018.11.655
发表时间：
2018-09-29
期刊：
Microbial cell (Graz, Austria)
影响因子：
--
作者：
Coccetti P;Nicastro R;Tripodi F
通讯作者：
Tripodi F
影响因子：
4.3
作者：
Beyer A;Workman C;Hollunder J;Radke D;Möller U;Wilhelm T;Ideker T
通讯作者：
Ideker T
影响因子：
4.8
作者：
García-Gimeno, MA;Muñoz, I;Sanz, P
通讯作者：
Sanz, P
影响因子：
9.2
作者：
Cherkasov, Valeria;Hofmann, Sarah;Bukau, Bernd
通讯作者：
Bukau, Bernd
压力依赖性的固定在动力学和空间上与p-bodies不同的细胞质颗粒的重新定位。
影响因子：
7.8
作者：
Hoyle, Nathaniel P.;Castelli, Lydia M.;Campbell, Susan G.;Holmes, Leah E. A.;Ashe, Mark P.
通讯作者：
Ashe, Mark P.