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

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.6K
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...
2.6K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

3.9K
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...
3.9K
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

3.9K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.9K
The Unfolded Protein Response01:37

The Unfolded Protein Response

5.1K
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...
5.1K
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

5.7K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.7K
Protein Modifications in the RER01:26

Protein Modifications in the RER

5.7K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.7K

You might also read

Related Articles

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

Sort by
Same author

A Glimpse into the Initial Microsecond of Biomolecular Condensation.

Journal of the American Chemical Society·2026
Same author

Cellular water-potential sensing through biomolecular condensation.

Nature·2026
Same author

Distinct RNA Physical Microenvironments Shape Unique Properties and Functions within Biomolecular Condensates.

Journal of the American Chemical Society·2026
Same author

Bridging hydrogen-bond-stabilized polymeric coacervate core micelles for high-efficiency drug encapsulation and delivery.

Nature communications·2026
Same author

Time-Resolved Genetically Encoded Indicators toward Quantitative Imaging of Calcium Dynamics in Living Cells.

ACS sensors·2026
Same author

Dexter Energy Transfer Photocatalytic Microdissection of Amyloid Plaques in Alzheimer's Disease.

JACS Au·2026

Related Experiment Video

Updated: Sep 20, 2025

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
16:43

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells

Published on: February 18, 2014

13.1K

Endoplasmic Reticulum Stress Induces Liquid-Liquid Phase Separation of GRP78 and Modulates Protein Aggregation

Jiaqi Li1,2, Xiangyu Zi1, Jiabao Fang1

  • 1School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 1 Wenyuan Road, Nanjing, Jiangsu 210023, China.

ACS Sensors
|May 23, 2025
PubMed
Summary

Glucose-regulated protein 78 (GRP78) forms condensates under cellular stress, recruiting disease-linked proteins like SOD1(A4V). This liquid-liquid phase separation (LLPS) impacts protein aggregation, offering insights into neurodegenerative disease mechanisms.

Keywords:
endoplasmic reticulum stressfluorescence lifetime imagingliquid−liquid phase separationpolarity sensitivityprotein aggregation

More Related Videos

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
10:12

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity

Published on: June 14, 2024

2.1K
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

14.7K

Related Experiment Videos

Last Updated: Sep 20, 2025

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
16:43

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells

Published on: February 18, 2014

13.1K
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
10:12

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity

Published on: June 14, 2024

2.1K
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

14.7K

Area of Science:

  • Cell Biology
  • Neuroscience
  • Biochemistry

Background:

  • Abnormal protein aggregation is central to neurodegenerative diseases.
  • Glucose-regulated protein 78 (GRP78) is a key endoplasmic reticulum (ER) chaperone involved in protein folding and ER stress.
  • Recent evidence suggests GRP78 participates in liquid-liquid phase separation (LLPS), but its pathological role is unclear.

Purpose of the Study:

  • To investigate the functional implications of GRP78 liquid-liquid phase separation (LLPS) under endoplasmic reticulum (ER) stress.
  • To explore the interaction between GRP78 condensates and mutant SOD1 (SOD1(A4V)), a protein linked to amyotrophic lateral sclerosis.
  • To develop tools for visualizing GRP78 phase transitions and associated microenvironmental changes.

Main Methods:

  • Design and synthesis of novel fluorescent probes (ER-Pro and Agg-Pro) for GRP78 labeling and polarity sensing.
  • Utilizing fluorescence lifetime imaging microscopy (FLIM) and confocal microscopy.
  • Analyzing the recruitment of SOD1(A4V) into GRP78 condensates and monitoring aggregation dynamics.

Main Results:

  • GRP78 undergoes liquid-liquid phase separation (LLPS) in response to endoplasmic reticulum (ER) stress.
  • GRP78 condensates recruit the amyotrophic lateral sclerosis-associated mutant SOD1(A4V), influencing its aggregation.
  • SOD1(A4V) aggregation correlates with local polarity shifts, suggesting a role for GRP78 LLPS in protein quality control.

Conclusions:

  • GRP78 liquid-liquid phase separation (LLPS) is a dynamic process involved in the cellular response to ER stress.
  • GRP78 condensates can modulate the aggregation of disease-associated proteins like SOD1(A4V).
  • These findings offer new perspectives on ER homeostasis, neurodegenerative disease pathogenesis, and potential diagnostic/therapeutic strategies.