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

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...
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...
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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...
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...

You might also read

Related Articles

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

Sort by
Same author

Targeting endoplasmic reticulum export disrupts metabolic resilience in multiple myeloma.

Signal transduction and targeted therapy·2026
Same author

Time reversal breaking of colloidal particles in cells.

The Journal of chemical physics·2026
Same author

Nascent protein retention at polysomes reduces kinetic barriers to self-assembly.

bioRxiv : the preprint server for biology·2026
Same author

Quiescence improves <i>Candida albicans</i> survival of fungicidal drug exposure.

bioRxiv : the preprint server for biology·2026
Same author

Transcriptional consequences of herpes simplex virus 1 ICP4 inducible expression in uninfected cells.

bioRxiv : the preprint server for biology·2025
Same author

TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence.

The EMBO journal·2025

Related Experiment Video

Updated: Jul 12, 2026

Split-Luciferase Reassembly Assay to Measure Endoplasmic Reticulum-Mitochondria Contacts in Live Cells
09:09

Split-Luciferase Reassembly Assay to Measure Endoplasmic Reticulum-Mitochondria Contacts in Live Cells

Published on: October 11, 2024

Mechanosensing at the endoplasmic reticulum by IRE1.

Hesso Farhan1, Michaela Mayr1, Luiz Garcia-Souza2

  • 1Institute of Pathophysiology, Medical University of Innsbruck, Innsbruck, Austria.

Research Square
|July 10, 2026
PubMed
Summary

The endoplasmic reticulum (ER) is a mechanosensitive organelle, with IRE1 acting as a sensor. Mechanical forces activate IRE1, enhancing protein synthesis and muscle force, independent of the unfolded protein response.

More Related Videos

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
10:12

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
13:40

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms

Published on: July 7, 2011

Related Experiment Videos

Last Updated: Jul 12, 2026

Split-Luciferase Reassembly Assay to Measure Endoplasmic Reticulum-Mitochondria Contacts in Live Cells
09:09

Split-Luciferase Reassembly Assay to Measure Endoplasmic Reticulum-Mitochondria Contacts in Live Cells

Published on: October 11, 2024

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
10:12

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
13:40

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms

Published on: July 7, 2011

Area of Science:

  • Cell Biology
  • Mechanobiology
  • Molecular Biology

Background:

  • Cellular mechanical force sensing is crucial for cell function.
  • Traditionally, the plasma membrane and nucleus are considered primary mechanosensors.
  • The role of other organelles in mechanotransduction remains less understood.

Purpose of the Study:

  • To identify novel mechanosensitive organelles within eukaryotic cells.
  • To investigate the role of the endoplasmic reticulum (ER) in sensing mechanical forces.
  • To uncover the molecular mechanisms linking mechanical stimuli to cellular responses.

Main Methods:

  • Applying mechanical forces to ER membranes in vitro.
  • Utilizing IRE1 as a candidate ER-resident mechanosensor.
  • Investigating signaling pathways downstream of IRE1 activation, including JNK signaling and protein synthesis.
  • Analyzing IRE1 activation and protein translation in engineered skeletal muscle tissue under mechanical stimulation.

Main Results:

  • The endoplasmic reticulum (ER) functions as an autonomous mechanosensitive organelle.
  • IRE1, an ER-resident protein, acts as a direct mechanosensor, detecting membrane tension.
  • Mechanical activation of IRE1 triggers JNK signaling and increases global protein synthesis, independent of the unfolded protein response (UPR) and XBP1 splicing.
  • Electrical stimulation and passive stretch in skeletal muscle tissue activate IRE1, boost translation, and enhance contractile force.

Conclusions:

  • Uncovered a non-canonical role for IRE1 as an ER-based mechanosensor.
  • Demonstrated that IRE1 couples mechanical forces to the regulation of protein translation.
  • Established a novel pathway for mechanotransduction originating from the ER, impacting cellular functions like muscle adaptation.