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Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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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...
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The Unfolded Protein Response01:37

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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...
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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.
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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.
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Directing Proteins to the Rough Endoplasmic Reticulum01:34

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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...
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In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
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Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
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Inositol Requiring Enzyme (IRE), a multiplayer in sensing endoplasmic reticulum stress.

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  • 1Department of Biochemistry, University of Alberta, Edmonton, Canada.

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|January 21, 2022
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The endoplasmic reticulum (ER) stress sensor IRE1α, crucial for cellular homeostasis, has diverse roles. It interacts with various proteins and organelle membranes to manage cellular stress responses.

Keywords:
IRE1αendoplasmic reticulumstress sensorunfolded protein response

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Stress Response

Background:

  • The endoplasmic reticulum (ER) detects cellular stress and initiates adaptive responses like the unfolded protein response (UPR).
  • The UPR involves three key sensors: IRE1α, PERK, and ATF6, which restore ER homeostasis.
  • IRE1α is an ancient UPR pathway conserved across plant and animal cells.

Purpose of the Study:

  • To elucidate the multifunctional roles of IRE1α in cellular stress management.
  • To explore the interactions and localization of IRE1α within the cell.

Main Methods:

  • Proteomic analysis to identify ER luminal and cytosolic interactomes of IRE1α.
  • Investigating IRE1α's association with organellar membrane contact sites.

Main Results:

  • IRE1α possesses both kinase and nuclease activities essential for ER stress response.
  • Identification of extensive ER luminal and cytosolic interaction networks for IRE1α.
  • IRE1α's involvement in organellar membrane contacts facilitates inter-organelle communication during stress.

Conclusions:

  • IRE1α is a multifunctional ER stress sensor with a broad impact on cellular processes.
  • Understanding IRE1α's interactome and localization provides insights into its regulatory mechanisms.
  • IRE1α's role in organellar contacts highlights its importance in coordinating cellular responses to stress.