Related Experiment Video
Updated: Jul 17, 2025
10:12
Visualization of G3BP Stress Granules Dynamics in Live Primary Cells
Published on: May 21, 2014
18.4K
The RasGAP-associated endoribonuclease G3BP mediates stress granule assembly
Hélène Tourrière1, Karim Chebli1, Latifa Zekri1
1Institut de Génétique Moléculaire de Montpellier, UMR 5535 du Centre National de la Recherche Scientifique (CNRS), Université Montpellier, Montpellier, France.
The Journal of Cell Biology
|September 6, 2023
Summary
Stress granules (SGs) are cytoplasmic protein aggregates crucial for mRNA regulation. This study reveals G3BP protein as a key effector in SG assembly, influenced by Ras signaling and phosphorylation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Stress granules (SGs) are cytoplasmic foci formed under cellular stress.
- SGs regulate mRNA metabolism, influencing translation and degradation.
- The precise molecular mechanisms governing SG assembly remain incompletely understood.
Purpose of the Study:
- To investigate the role of G3BP protein in stress granule assembly.
- To elucidate the involvement of Ras signaling in stress granule formation.
- To determine how G3BP phosphorylation affects stress granule dynamics.
Main Methods:
- Cellular stress induction using arsenite.
- Overexpression and domain-specific expression of G3BP.
- Analysis of G3BP recruitment to stress granules.
- Site-directed mutagenesis of G3BP phosphorylation sites.
Main Results:
- G3BP is recruited to stress granules upon arsenite exposure.
- G3BP overexpression induces SG assembly, while a G3BP central domain inhibits it.
- Dephosphorylation of G3BP at serine 149 is induced by arsenite.
- A non-phosphorylatable G3BP mutant (S149A) robustly assembles SGs.
Conclusions:
- G3BP acts as a critical effector protein in stress granule assembly.
- Ras signaling pathway regulates G3BP dephosphorylation, impacting SG formation.
- G3BP phosphorylation status is a key determinant of stress granule dynamics.
Related Concept Videos
01:24Small GTPases - Ras and Rho
4.0K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.0K
01:31Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
01:33Coat Assembly and GTPases
3.6K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.6K
01:37The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
01:25Rab Cascades
2.7K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.7K
01:32Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K