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Related Concept Videos

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

Protein Folding Quality Check in the RER

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...
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...

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Related Experiment Video

Updated: Jun 10, 2026

Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum
07:49

Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum

Published on: January 22, 2019

Modeling the endoplasmic reticulum unfolded protein response.

Amos Onn, David Ron

    Nature Structural & Molecular Biology
    |August 5, 2010
    PubMed
    Summary

    A new quantitative model explains how inositol-requiring enzyme 1 (IRE1) is activated by endoplasmic reticulum stress. This model resolves a long-standing scientific debate regarding IRE1 signaling mechanisms.

    Area of Science:

    • Molecular biology
    • Cellular signaling
    • Biophysics

    Background:

    • Endoplasmic reticulum (ER) stress is a critical cellular condition.
    • Inositol-requiring enzyme 1 (IRE1) is a key sensor of ER stress.
    • The precise mechanism of IRE1 activation has been debated.

    Discussion:

    • This study presents a quantitative model for IRE1 signaling.
    • The model elucidates the step-by-step activation process of IRE1.
    • It addresses and resolves a persistent controversy in the field.

    Key Insights:

    • The quantitative model provides a mechanistic understanding of IRE1 activation.
    • It clarifies the role of specific molecular events in IRE1 signaling.
    • The findings offer new perspectives on how cells respond to ER stress.

    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
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    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

    Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
    16:43

    Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells

    Published on: February 18, 2014

    Related Experiment Videos

    Last Updated: Jun 10, 2026

    Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum
    07:49

    Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum

    Published on: January 22, 2019

    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

    Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
    16:43

    Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells

    Published on: February 18, 2014

    Outlook:

    • Further experimental validation of the model is warranted.
    • The model could be extended to other stress response pathways.
    • This work may inform therapeutic strategies targeting ER stress.