Related Experiment Video
Updated: Jun 6, 2025
12:38
Using Caenorhabditis elegans as a Model System to Study Protein Homeostasis in a Multicellular Organism
Published on: December 18, 2013
6.1K
ER quality control through reticulophagy and protein secretion
Cathena Meiling Li1, Yong-Keun Jung1
1School of Biological Sciences, Seoul National University, Seoul, Korea.
Autophagy
|November 27, 2024
Summary
Researchers discovered that the protein FKBPL regulates reticulophagy, the process of clearing endoplasmic reticulum (ER) components. The FKBPL-CKAP4 interaction is key for ER quality control and influences protein secretion.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy
Background:
- The endoplasmic reticulum (ER) is vital for cellular functions and homeostasis.
- Maintaining ER quality control is essential for cell survival.
Purpose of the Study:
- To identify novel regulators of reticulophagy, the selective autophagy of the ER.
- To elucidate the molecular mechanism by which FKBPL controls reticulophagy and protein secretion.
Main Methods:
- A morphology-based gain-of-function screen was employed to identify FKBPL.
- Protein-binding assays and cellular imaging were used to study the FKBPL-CKAP4 interaction.
- Investigated the impact of FKBPL-CKAP4 axis disruption on reticulophagy and protein secretion.
Main Results:
- FKBPL was identified as a cytosolic regulator of reticulophagy.
- FKBPL binds to ER-resident CKAP4, bridging the ER to the phagophore for lysosomal degradation.
- The FKBPL-CKAP4 axis is crucial for both basal and stress-induced reticulophagy.
- Disruption of the FKBPL-CKAP4 interaction impairs reticulophagy and increases protein secretion via microvesicles.
Conclusions:
- The FKBPL-CKAP4 axis plays a critical role in regulating reticulophagy.
- This axis also influences cellular protein secretion pathways.
- FKBPL-CKAP4 has a dual function in ER quality control and protein secretion.
Related Concept Videos
01:29Protein Folding Quality Check in the RER
3.7K
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...
3.7K
01:32Export of Misfolded Proteins out of the ER
3.5K
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...
3.5K
01:45ER Retrieval Pathway
3.8K
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...
3.8K
01:27Post-translational Translocation of Proteins to the RER
5.6K
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...
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...
5.6K
01:20Cotranslational Protein Translocation
7.2K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.2K
00:58Recycling Endosomes and Transcytosis
2.6K
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
2.6K