Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
The Unfolded Protein Response01:37

The Unfolded Protein Response

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...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Single-nuclei UPR profiling by flow cytometry reveals bortezomib resistance mechanisms in multiple myeloma.

EMBO molecular medicine·2026
Same author

Allosteric disordering of eIF2B regulates the integrated stress response.

Nature chemical biology·2026
Same author

STING dampens the unfolded protein response to enable the presentation of self-antigens on MHC-I during inflammation.

Cell reports·2026
Same author

Harnessing viral strategies to reverse cognitive dysfunction through the integrated stress response.

Science (New York, N.Y.)·2026
Same author

CELF1 is a non-canonical eIF4E binding protein that promotes translation of epithelial-mesenchymal transition effector mRNAs.

Nucleic acids research·2026
Same author

VPS34-IN1 potentiates STING-dependent activation in human CAL-1 cells.

Cellular & molecular biology letters·2026
Same journal

Mechanisms underpinning chromosome structure in metazoans.

Molecular biology of the cell·2026
Same journal

Conserved and Divergent Modes of Substrate Interaction Define Selective Localizations and Functions of a Cdc14 Phosphatase.

Molecular biology of the cell·2026
Same journal

Dimerization of the centriolin-like protein Nud1 governs spindle pole body inheritance in budding yeast.

Molecular biology of the cell·2026
Same journal

Non-muscle Myosin II acts as a negative feedback mediator to control cell contraction dynamics in adherent cells.

Molecular biology of the cell·2026
Same journal

The tetraspanin disc proteins, peripherin-2 and ROM1, facilitate CNG channel localization to the rod outer segment.

Molecular biology of the cell·2026
Same journal

Csf1 facilitates adaptive membrane lipid remodeling linked to ER-plasma membrane contact sites.

Molecular biology of the cell·2026
See all related articles

Related Experiment Video

Updated: May 20, 2026

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells
10:12

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells

Published on: May 21, 2014

Large G3BP-induced granules trigger eIF2α phosphorylation.

Lucas C Reineke1, Jon D Dougherty, Philippe Pierre

  • 1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77584, USA.

Molecular Biology of the Cell
|July 27, 2012
PubMed
Summary
This summary is machine-generated.

Stress granules, mRNP aggregates, actively signal to the cell. Large stress granule assembly triggers protein kinase R to phosphorylate eIF2α, repressing translation.

More Related Videos

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
09:33

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules

Published on: May 12, 2017

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Related Experiment Videos

Last Updated: May 20, 2026

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells
10:12

Visualization of G3BP Stress Granules Dynamics in Live Primary Cells

Published on: May 21, 2014

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
09:33

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules

Published on: May 12, 2017

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Area of Science:

  • Cellular stress response
  • Molecular biology
  • RNA biology

Background:

  • Stress granules are cytoplasmic mRNP aggregates formed during cellular stress.
  • They are traditionally viewed as inert storage sites for silenced mRNAs.
  • Their role in active cellular signaling remains incompletely understood.

Purpose of the Study:

  • To investigate the signaling capacity of stress granules during their assembly.
  • To determine the relationship between stress granule size and translational control.
  • To identify the specific kinase responsible for eIF2α phosphorylation induced by stress granules.

Main Methods:

  • Overexpression of G3BP to induce stress granule formation.
  • Analysis of stress granule assembly dynamics and eIF2α phosphorylation.
  • Utilizing mouse embryonic fibroblasts deficient in specific eIF2α kinases.

Main Results:

  • Large G3BP-induced stress granules, but not small ones, precede eIF2α phosphorylation.
  • Protein kinase R (PKR) was identified as the primary kinase mediating eIF2α phosphorylation.
  • Stress granule size appears to correlate with a threshold for triggering translational repression.

Conclusions:

  • Stress granules are not inert but actively signal to the translational machinery.
  • Stress granule assembly size is a critical factor in initiating the eIF2α phosphorylation-mediated translational repression.
  • These findings suggest a novel role for stress granules in regulating the innate immune response.