| Autor: |
Dawid Krokowski, Raul Jobava, Krzysztof J. Szkop, Chien-Wen Chen, Xu Fu, Sarah Venus, Bo-Jhih Guan, Jing Wu, Zhaofeng Gao, Wioleta Banaszuk, Marek Tchorzewski, Tingwei Mu, Phil Ropelewski, William C. Merrick, Yuanhui Mao, Aksoylu Inci Sevval, Helen Miranda, Shu-Bing Qian, Maria Manifava, Nicholas T. Ktistakis, Anastasios Vourekas, Eckhard Jankowsky, Ivan Topisirovic, Ola Larsson, Maria Hatzoglou |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell reports. 40(3) |
| ISSN: |
2211-1247 |
| Popis: |
The integrated stress response (ISR) plays a pivotal role in adaptation of translation machinery to cellular stress. Here, we demonstrate an ISR-independent osmoadaptation mechanism involving reprogramming of translation via coordinated but independent actions of mTOR and plasma membrane amino acid transporter SNAT2. This biphasic response entails reduced global protein synthesis and mTOR signaling followed by translation of SNAT2. Induction of SNAT2 leads to accumulation of amino acids and reactivation of mTOR and global protein synthesis, paralleled by partial reversal of the early-phase, stress-induced translatome. We propose SNAT2 functions as a molecular switch between inhibition of protein synthesis and establishment of an osmoadaptive translation program involving the formation of cytoplasmic condensates of SNAT2-regulated RNA-binding proteins DDX3X and FUS. In summary, we define key roles of SNAT2 in osmotolerance. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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