title: Large G3BP-induced granules trigger eIF2α phosphorylation.
abstract: Stress granules are large messenger ribonucleoprotein (mRNP) aggregates composed of translation initiation factors and mRNAs that appear when the cell encounters various stressors. Current dogma indicates that stress granules function as inert storage depots for translationally silenced mRNPs until the cell signals for renewed translation and stress granule disassembly. We used RasGAP SH3-binding protein (G3BP) overexpression to induce stress granules and study their assembly process and signaling to the translation apparatus. We found that assembly of large G3BP-induced stress granules, but not small granules, precedes phosphorylation of eIF2α. Using mouse embryonic fibroblasts depleted for individual eukaryotic initiation factor 2α (eIF2α) kinases, we identified protein kinase R as the principal kinase that mediates eIF2α phosphorylation by large G3BP-induced granules. These data indicate that increasing stress granule size is associated with a threshold or switch that must be triggered in order for eIF2α phosphorylation and subsequent translational repression to occur. Furthermore, these data suggest that stress granules are active in signaling to the translational machinery and may be important regulators of the innate immune response.
authors: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77584, USA.
authors: Lucas C
authors: LC
authors: Reineke
authors: Jon D
authors: JD
authors: Dougherty
authors: Philippe
authors: P
authors: Pierre
authors: Richard E
authors: RE
authors: Lloyd
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009154:Mutation; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D014176:Protein Biosynthesis / Q000235:genetics; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D015852:Eukaryotic Initiation Factor-2; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; D049452:Green Fluorescent Proteins; D019892:eIF-2 Kinase; D004265:DNA Helicases; C116070:G3BP1 protein, human; C492055:G3bp1 protein, mouse; D020365:RNA Helicases