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Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
Protein quality control in the early secretory pathway
Tiziana Anelli1, Roberto Sitia
1Department of Functional Genomics and Molecular Biology, Università Vita-Salute San Raffaele Scientific Institute, DiBiT-HSR, Milano, Italy.
The EMBO Journal
|January 25, 2008
Summary
Eukaryotic cells use sophisticated chaperone networks to ensure correct protein folding and transport. These systems, including public and private chaperones, operate at the endoplasmic reticulum-Golgi interface for efficient protein secretion.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Eukaryotic cells possess mechanisms to distinguish native from non-native proteins.
- Protein quality control is crucial, particularly for secretory proteins handled at the endoplasmic reticulum (ER)-Golgi interface.
Purpose of the Study:
- To elucidate novel molecular mechanisms governing protein maturation and transport in the early secretory pathway.
- To understand the roles of chaperone networks in protein quality control.
Main Methods:
- Analysis of chaperone networks involved in protein folding and maturation.
- Investigation of protein transport checkpoints along the secretory pathway.
- Characterization of 'public' and 'private' chaperone functions.
Main Results:
- Multiple chaperone networks collaborate to assist complex protein maturation.
- Chaperones are selectively induced to meet varying protein synthesis demands.
- 'Public' chaperones act on broad substrates, while 'private' chaperones are substrate-specific.
- Sequential checkpoints enhance efficiency and fidelity in protein secretion.
Conclusions:
- The early secretory pathway employs intricate chaperone systems for precise protein handling.
- Coordinated action of diverse chaperones and checkpoints ensures high-fidelity protein secretion.
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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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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
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01:33Overview of Secretory Vesicles
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01:20Cotranslational Protein Translocation
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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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