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Derlin-3 Is Required for Changes in ERAD Complex Formation under ER Stress
Yuka Eura1, Toshiyuki Miyata1,2, Koichi Kokame1
1Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan.
International Journal of Molecular Sciences
|August 30, 2020
Summary
Derlin-3, found only in the pancreas, is crucial for the endoplasmic reticulum (ER)-associated protein degradation (ERAD) system. Its absence disrupts protein quality control during ER stress.
Area of Science:
- Cellular Biology
- Molecular Biology
- Protein Degradation
Background:
- Endoplasmic reticulum (ER)-associated protein degradation (ERAD) is vital for clearing misfolded proteins.
- ERAD functions through cooperative complexes of ER-associated and luminal proteins.
Purpose of the Study:
- To investigate the role of Derlin-3 in the ERAD system.
- To understand how Derlin-3 influences ERAD complex composition and function.
Main Methods:
- Coimmunoprecipitation assays.
- Sucrose density gradient centrifugation.
- Analysis of mouse tissues (liver, pancreas, kidney) from different genotypes.
Main Results:
- Derlin-3 is exclusively expressed in the pancreas.
- Derlin-3 deficiency destabilizes Herp and causes ERAD substrate accumulation.
- ER stress induces shifts in ERAD complex composition, involving Derlin proteins.
- Derlin-3 deficiency impairs the transition of Derlin-2 between complexes under ER stress, particularly in the pancreas.
Conclusions:
- ERAD complex composition is tissue-specific and dynamically regulated by ER stress in a Derlin-3-dependent manner.
- Derlin-3 plays a critical role in adapting ERAD complex composition to manage ER stress.
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