TORC2 mediates the heat stress response in Drosophila by promoting the formation of stress granules.
TORC2 mediates the heat stress response in Drosophila by promoting the formation of stress granules.
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TORC2通过促进应激颗粒的形成来介导果蝇中的热应力反应。
DOI：
10.1242/jcs.168724
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发表时间：
2015-07-15
影响因子：
4
通讯作者：
Rabouille C
中科院分区：
文献类型：
--
作者：
Jevtov I;Zacharogianni M;van Oorschot MM;van Zadelhoff G;Aguilera-Gomez A;Vuillez I;Braakman I;Hafen E;Stocker H;Rabouille C
TOR激酶存在于两种复合物中，TORC 1参与生长控制，TORC 2的作用不太明确。在这里，我们询问TORC 2是否在维持细胞应激中发挥作用。我们表明，TORC2抑制果蝇导致热应激的耐受性降低，而对其他压力的敏感性不受影响。因此，我们表明，在热应激时，在动物和果蝇培养的S2细胞中，TORC 2被激活，并且是维持其已知靶点Akt1（也称为PKB）水平所必需的。我们发现，应激活化蛋白激酶的磷酸化不受TORC 2的调节，也不是热诱导的热休克蛋白的上调。相反，我们表明，在体内和培养的细胞中，TORC 2是热诱导的细胞保护性核糖核蛋白颗粒，促生存应激颗粒的组装所需的。这些颗粒是响应于热应激所施加的蛋白质翻译抑制而形成的，热应激在缺乏TORC 2功能的情况下似乎效率较低。我们建议，TORC 2介导的果蝇的耐热性，通过促进细胞自主形成的应力颗粒。突出显示的文章：果蝇TOR复合物2是热诱导的细胞保护应激颗粒形成所必需的，这可以解释TORC 2突变果蝇的热敏感性。
The kinase TOR is found in two complexes, TORC1, which is involved in growth control, and TORC2, whose roles are less well defined. Here, we asked whether TORC2 has a role in sustaining cellular stress. We show that TORC2 inhibition in Drosophila melanogaster leads to a reduced tolerance to heat stress, whereas sensitivity to other stresses is not affected. Accordingly, we show that upon heat stress, both in the animal and Drosophila cultured S2 cells, TORC2 is activated and is required for maintaining the level of its known target, Akt1 (also known as PKB). We show that the phosphorylation of the stress-activated protein kinases is not modulated by TORC2 nor is the heat-induced upregulation of heat-shock proteins. Instead, we show, both in vivo and in cultured cells, that TORC2 is required for the assembly of heat-induced cytoprotective ribonucleoprotein particles, the pro-survival stress granules. These granules are formed in response to protein translation inhibition imposed by heat stress that appears to be less efficient in the absence of TORC2 function. We propose that TORC2 mediates heat resistance in Drosophila by promoting the cell autonomous formation of stress granules. Highlighted Article: The Drosophila TOR complex 2 is necessary for the formation of heat-induced cytoprotective stress granules, which can explain the heat sensitivity of TORC2 mutant flies.