Stress granules sense metabolic stress at the plasma membrane and potentiate recovery by storing active Pkc1

Stress granules sense metabolic stress at the plasma membrane and potentiate recovery by storing active Pkc1
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DOI:
10.1126/scisignal.aaz6339
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发表时间:
2020-03-17
期刊:
影响因子:
7.3
通讯作者:
Kaganovich, Daniel
Kaganovich, Daniel
中科院分区:
生物学1区
文献类型:
--
作者:
Amen, Triana;Kaganovich, Daniel

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作为细胞与外界环境之间的物理屏障,质膜处于良好的位置,成为应激的第一反应器。膜也非常容易受到许多类型的扰动,包括热、力、渗透压、脂质短缺和饥饿。为了确定营养胁迫引起的酿酒酵母质膜结构变化是否可以传达给细胞内的调控网络,我们鉴定了与胁迫颗粒(SGs)相互作用的蛋白质,由蛋白质组成的亚细胞结构,以及当细胞受到胁迫时形成的非翻译RNA。我们发现,SG蛋白相互作用的eisosomes,这是一个独特的脂质和蛋白质组成的皮质下膜结构的组件。为了响应饥饿触发的eisosome蛋白的磷酸化,eisosomes聚集和招募SG组件,包括活性Pkc1。不存在的eisosomes受损SG的形成,导致延迟恢复营养剥夺。因此,eisosome聚类是一个例子域间通信响应压力,并确定了一个以前未知的SG调节机制。
As the physical barrier between the cell and the outside environment, the plasma membrane is well-positioned to be the first responder to stress. The membrane is also highly vulnerable to many types of perturbation, including heat, force, osmotic pressure, lipid shortage, and starvation. To determine whether the structural changes in the plasma membrane of Saccharomyces cerevisiae brought about by nutrient stress can be communicated to regulatory networks within the cell, we identified proteins that interact with stress granules (SGs), subcellular structures composed of proteins, and nontranslated RNAs that form when cells are stressed. We found that SG proteins interacted with components of eisosomes, which are subcortical membrane structures with a distinct lipid and protein composition. In response to starvation-triggered phosphorylation of eisosome proteins, eisosomes clustered and recruited SG components, including active Pkc1. The absence of eisosomes impaired SG formation, resulting in delayed recovery from nutrient deprivation. Thus, eisosome clustering is an example of interdomain communication in response to stress and identifies a previously unknown mechanism of SG regulation.