Related Experiment Video
Updated: Jul 11, 2026
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
How transmembrane proteins sense endoplasmic reticulum stress
1Department of Cell Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, Nara, Japan. kkouno@bs.naist.jp
Antioxidants & Redox Signaling
|September 28, 2007
Summary
The unfolded protein response (UPR) helps cells recover from endoplasmic reticulum (ER) stress. This review details how ER stress sensors like IRE1, PERK, and ATF6 recognize unfolded proteins to initiate the UPR.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Biochemistry
Background:
- The unfolded protein response (UPR) is a critical cellular mechanism for maintaining endoplasmic reticulum (ER) homeostasis.
- Accumulation of unfolded or misfolded proteins in the ER triggers the UPR.
- The UPR involves conserved signaling pathways to restore ER function.
Purpose of the Study:
- To review current understanding of how ER stress sensors detect unfolded proteins.
- To elucidate the recognition mechanisms of IRE1, PERK, and ATF6 pathways.
- To highlight progress in understanding the initiation of the UPR.
Main Methods:
- Literature review of UPR research.
- Analysis of molecular mechanisms of ER stress sensing.
- Comparative study of UPR pathways across eukaryotes.
Main Results:
- The UPR involves three main pathways: IRE1, PERK, and ATF6.
- These pathways are initiated by transmembrane ER stress sensors.
- Unfolded proteins are recognized within the ER lumen by these sensors.
Conclusions:
- The IRE1, PERK, and ATF6 pathways are central to the UPR.
- ER stress sensors play a crucial role in detecting misfolded proteins.
- Further research is needed to fully understand these recognition events.
Related Concept Videos
01:26Insertion of Single-pass Transmembrane Proteins in the RER
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
01:31Regulation 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...
01:34Directing 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...
01:27Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
01:28Protein 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.
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.
01:37The 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...