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Related Concept Videos

Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

6.5K
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...
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The Unfolded Protein Response01:37

The Unfolded Protein Response

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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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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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Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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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...
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Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

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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...
7.0K
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

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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...
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Endoplasmic reticulum stress in biological processing and disease.

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Cellular protein folding relies on the endoplasmic reticulum (ER), where stress triggers the unfolded protein response (UPR). This review explores ER stress, UPR, and their links to chronic diseases like diabetes and neurodegeneration.

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Pathophysiology

Background:

  • Proper protein folding within the endoplasmic reticulum (ER) is crucial for cellular function.
  • ER stress, caused by factors like infections or mutations, disrupts protein homeostasis, leading to misfolded protein accumulation.
  • The unfolded protein response (UPR) is a cellular defense mechanism against ER stress.

Purpose of the Study:

  • To review the current understanding of the relationship between ER stress, UPR, and chronic diseases.
  • To elucidate the pathophysiological links between ER dysfunction and diseases such as diabetes, neurodegenerative disorders, fatty liver disease, and inflammatory bowel disease.

Main Methods:

  • Literature review of scientific articles on ER stress, UPR, and chronic diseases.
  • Synthesis of information on biological processing, cellular responses to stress, and disease mechanisms.

Main Results:

  • ER stress and UPR are implicated in the pathophysiology of several chronic diseases.
  • Dysregulated UPR and prolonged ER stress can result in apoptosis and inflammation.
  • The precise pathophysiological roles in diseases like diabetes and neurodegenerative disorders require further elucidation.

Conclusions:

  • ER stress and UPR are significant factors in the development and progression of various chronic diseases.
  • Understanding these pathways offers potential therapeutic targets for managing chronic conditions.
  • Further research is needed to fully clarify the pathophysiological mechanisms linking ER stress to specific chronic diseases.