Related Experiment Video
Updated: Dec 21, 2025
10:56
Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
12.4K
Endoplasmic Reticulum Protein Quality Control in β Cells
Neha Shrestha1, Rachel B Reinert2, Ling Qi3
1Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Seminars in Cell & Developmental Biology
|May 14, 2020
Summary
Diabetes impairs pancreatic beta cell function, crucial for glucose control. Endoplasmic reticulum (ER) protein quality control, including the unfolded protein response (UPR), ER-phagy, and ER-associated degradation (ERAD), is vital for beta cell health and may impact diabetes pathogenesis.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Type 1 and type 2 diabetes are characterized by pancreatic beta cell dysfunction.
- Beta cell function is critically dependent on maintaining protein homeostasis within the endoplasmic reticulum (ER).
Purpose of the Study:
- To review the roles of ER protein quality-control mechanisms in beta cells.
- To explore how these mechanisms contribute to beta cell function, survival, and identity.
- To understand their implications in diabetes pathogenesis.
Main Methods:
- Literature review of endoplasmic reticulum protein quality control.
- Analysis of the unfolded protein response (UPR) in beta cells.
- Examination of autophagy (ER-phagy) and ER-associated degradation (ERAD) in beta cells.
Main Results:
- The unfolded protein response (UPR) is a key ER stress pathway.
- ER-phagy and ER-associated degradation (ERAD) are crucial for clearing damaged ER proteins.
- These quality control systems are essential for maintaining beta cell function and survival.
Conclusions:
- Dysregulation of ER protein quality control contributes to beta cell loss in diabetes.
- Different quality control pathways may govern distinct aspects of beta cell biology.
- Targeting ER quality control mechanisms offers potential therapeutic strategies for diabetes.
Related Concept Videos
01:29Protein Folding Quality Check in the RER
4.9K
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...
4.9K
01:37The Unfolded Protein Response
6.1K
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...
6.1K
01:17Role of ER in the Secretory Pathway
6.7K
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...
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...
6.7K
01:32Export of Misfolded Proteins out of the ER
4.8K
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...
4.8K
01:26Protein Modifications in the RER
6.6K
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.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
6.6K
01:45ER Retrieval Pathway
4.5K
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.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
4.5K