Research ArticleCell Biology

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

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Science Signaling  17 Mar 2020:
Vol. 13, Issue 623, eaaz6339
DOI: 10.1126/scisignal.aaz6339

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Stress granule nucleation at the membrane

In response to stress, eukaryotic cells produce clusters of proteins and RNAs called stress granules (SGs), which sequester mRNAs from the translation machinery until the stress is resolved and may also regulate cellular stress response pathways. Amen and Kaganovich found that, in yeast, SG proteins interacted with components of subcortical structures called eisosomes, which are composed of specific proteins and membrane lipids. Upon starvation, eisosomes clustered and promoted the formation of SGs. Pkc1 (the yeast isoform of protein kinase C) was required for starvation-induced eisosome reorganization and was recruited to SGs in its active form. In the absence of eisosomes, active Pkc1 was not retained in SGs, and recovery from starvation was delayed. These findings identify a mechanism whereby nutrient stress induces structural changes at the plasma membrane that promote the formation of SGs, thus protecting the cell during stress and enabling faster recovery.

Abstract

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.

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