Related Experiment Video
Updated: Oct 9, 2025
16:43
Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
Published on: February 18, 2014
13.2K
Protein Aggregation in the ER: Calm behind the Storm
Haisen Li1, Shengyi Sun1,2
1Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cells
|December 24, 2021
Summary
The endoplasmic reticulum (ER) maintains protein homeostasis through quality control. Defects in these systems cause ER storage diseases due to misfolded protein accumulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The endoplasmic reticulum (ER) is crucial for protein synthesis, folding, and assembly in eukaryotic cells.
- ER homeostasis is maintained by chaperones and quality control pathways safeguarding protein biogenesis.
- Misfolded proteins can accumulate, leading to ER storage diseases if not cleared efficiently.
Purpose of the Study:
- To review the protein folding and quality control networks within the ER.
- To survey recent research on ER storage diseases and the role of ER quality control.
- To discuss current challenges and future directions in the field.
Main Methods:
- Literature review of protein folding and quality control mechanisms.
- Analysis of research on ER storage diseases.
- Synthesis of information on chaperones, UPR, ERAD, and ER-phagy.
Main Results:
- Detailed summary of ER protein folding and quality control systems (chaperones, UPR, ERAD, ER-phagy).
- Overview of ER storage diseases, highlighting the impact of ER quality control defects.
- Identification of key research advancements and remaining questions.
Conclusions:
- ER quality control is essential for preventing misfolded protein aggregation and ER storage diseases.
- Understanding these pathways offers insights into disease mechanisms and potential therapeutic targets.
- Further research is needed to address outstanding questions and explore emerging concepts in ER homeostasis.
Related Concept Videos
01:32Export of Misfolded Proteins out of the ER
4.1K
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...
4.1K
01:29Protein Folding Quality Check in the RER
4.0K
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...
4.0K
01:27Post-translational Translocation of Proteins to the RER
6.1K
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...
6.1K
01:45Tail-anchoring of Proteins in the ER Membrane
3.2K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.2K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
11.6K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
11.6K
01:43The Endoplasmic Reticulum
16.2K
The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
16.2K