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J Cell Biol. 2016 Mar 28;212(7):845-60. doi: 10.1083/jcb.201508028.

G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits.

Author information

1
Division of Rheumatology, Immunology and Allergy, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115 nkedersha@rics.bwh.harvard.edu.
2
Division of Rheumatology, Immunology and Allergy, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115.
3
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
4
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm SE-171 77, Sweden.
5
Division of Rheumatology, Immunology and Allergy, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115 The Broad Institute of Harvard and MIT, Cambridge, MA 02142.

Abstract

Mammalian stress granules (SGs) contain stalled translation preinitiation complexes that are assembled into discrete granules by specific RNA-binding proteins such as G3BP. We now show that cells lacking both G3BP1 and G3BP2 cannot form SGs in response to eukaryotic initiation factor 2α phosphorylation or eIF4A inhibition, but are still SG-competent when challenged with severe heat or osmotic stress. Rescue experiments using G3BP1 mutants show that phosphomimetic G3BP1-S149E fails to rescue SG formation, whereas G3BP1-F33W, a mutant unable to bind G3BP partner proteins Caprin1 or USP10, rescues SG formation. Caprin1/USP10 binding to G3BP is mutually exclusive: Caprin binding promotes, but USP10 binding inhibits, SG formation. G3BP interacts with 40S ribosomal subunits through its RGG motif, which is also required for G3BP-mediated SG formation. We propose that G3BP mediates the condensation of SGs by shifting between two different states that are controlled by the phosphorylation of S149 and by binding to Caprin1 or USP10.

PMID:
27022092
PMCID:
PMC4810302
DOI:
10.1083/jcb.201508028
[Indexed for MEDLINE]
Free PMC Article

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