title: 5'-AMP-activated protein kinase alpha regulates stress granule biogenesis.
abstract: Stress granule (SG) assembly represents a conserved eukaryotic defense strategy against various insults. Although essential for the ability to cope with deleterious conditions, the signaling pathways controlling SG formation are not fully understood. The energy sensor AMP-activated protein kinase (AMPK) is critical for the cellular stress response. Human cells produce two AMPK catalytic α-subunits with not only partially overlapping, but also unique functions. Here, we provide direct support for structural and functional links between AMPK-α isoforms and SGs. As such, several stressors promote SG association of AMPK-α2, but not AMPK-α1. Multiple lines of evidence link AMPK activity to SG biogenesis. First, pharmacological kinase inhibition interfered with SG formation. Second, AMPK-α knockdown combined with in-depth quantitative SG analysis revealed isoform-specific changes of SG characteristics. Third, overexpression of mutant α-subunits further substantiated that AMPK regulates SG parameters. Finally, we identified the SG-nucleating protein G3BP1 as an AMPK-α2 binding partner. This interaction is stimulated by stress and notably occurs in SGs. Collectively, our data define the master metabolic regulator AMPK as a novel SG constituent that also controls their biogenesis.
authors.affiliation: Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.
authors.forename: Hicham
authors.initials: H
authors.lastname: Mahboubi
authors.affiliation: Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.
authors.forename: Ramla
authors.initials: R
authors.lastname: Barisé
authors.affiliation: Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada. Electronic address: ursula.stochaj@mcgill.ca.
authors.forename: Ursula
authors.initials: U
authors.lastname: Stochaj
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D004265:DNA Helicases; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding / Q000187:drug effects; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D013312:Stress, Physiological / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D004852:Epoxy Compounds; D007527:Isoenzymes; D018942:Macrolides; D050505:Mutant Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D013844:Thiazoles; C421324:pateamine A; D055372:AMP-Activated Protein Kinases; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases
keywords: 5′-AMP-activated protein kinase; Apoptosis; Oxidative stress; Quantitative microscopy; Signaling; Stress granules