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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cytoplasmic Granules / enzymology*
  • Cytoplasmic Granules / genetics
  • DNA Helicases
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-4A / metabolism
  • Humans
  • Microscopy, Confocal
  • Microscopy, Video
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Poly-ADP-Ribose Binding Proteins
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • RNA Helicases
  • RNA Interference
  • RNA Recognition Motif Proteins
  • RNA-Binding Proteins
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Ribosome Subunits, Small, Eukaryotic / genetics
  • Ribosome Subunits, Small, Eukaryotic / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship
  • Transfection
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*


  • Adaptor Proteins, Signal Transducing
  • CAPRIN1 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Eukaryotic Initiation Factor-2
  • G3BP2 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • USP10 protein, human
  • Eukaryotic Initiation Factor-4A
  • Ubiquitin Thiolesterase
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases