Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

5.0K
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...
5.0K
Oligosaccharide Assembly01:24

Oligosaccharide Assembly

3.5K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
3.5K
Protein Modifications in the RER01:26

Protein Modifications in the RER

6.9K
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...
6.9K
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

5.0K
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...
5.0K
ER Retrieval Pathway01:45

ER Retrieval Pathway

4.7K
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...
4.7K
The Unfolded Protein Response01:37

The Unfolded Protein Response

6.2K
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...
6.2K
  1. Home
  3. Research Domains
  5. Biological Sciences
  7. Industrial Biotechnology
  9. Bioprocessing, Bioproduction And Bioproducts
  11. Oligosaccharyltransferase Is Involved In Targeting To Er-associated Degradation

Oligosaccharyltransferase Is Involved in Targeting to ER-Associated Degradation

Marina Shenkman1,2, Navit Ogen-Shtern1, Chaitanya Patel1,2

  • 1The Shmunis School of Biomedicine and Cancer Research, Cell Biology Division, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

Cells
|October 28, 2025

Related Experiment Videos

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae
09:05

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

29.8K
Pulse-chase Analysis of N-linked Sugar Chains from Glycoproteins in Mammalian Cells
10:17

Pulse-chase Analysis of N-linked Sugar Chains from Glycoproteins in Mammalian Cells

Published on: April 27, 2010

15.6K
Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
10:57

Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae

Published on: February 16, 2015

10.1K

View abstract on PubMed

Summary
This summary is machine-generated.

The oligosaccharyltransferase (OST) complex, known for protein glycosylation, also aids in ER-associated degradation (ERAD). OST subunits interact with ERAD machinery, facilitating the removal of misfolded proteins.

Area of Science:

  • Cell Biology
  • Protein Biochemistry
  • Molecular Biology

Background:

  • N-glycosylation is a crucial post-translational modification for most secreted and membrane proteins, catalyzed by the oligosaccharyltransferase (OST) complex in the endoplasmic reticulum (ER).
  • Proteins that fail quality control in the ER are targeted for degradation through ER-associated degradation (ERAD) or ER-phagy.
  • Previous studies suggested roles for OST subunits beyond their catalytic function in glycosylation.

Purpose of the Study:

  • To investigate the potential involvement of OST subunits in ER-associated degradation (ERAD) of misfolded proteins.
  • To elucidate the mechanism by which OST might participate in ERAD pathways.

Main Methods:

  • Stable isotope labeling by amino acids in cell culture (SILAC) proteomics to identify protein interactors.
Keywords:
ERADHRD1OSTendoplasmic reticulum

Related Experiment Videos

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae
09:05

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

29.8K
Pulse-chase Analysis of N-linked Sugar Chains from Glycoproteins in Mammalian Cells
10:17

Pulse-chase Analysis of N-linked Sugar Chains from Glycoproteins in Mammalian Cells

Published on: April 27, 2010

15.6K
Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
10:57

Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae

Published on: February 16, 2015

10.1K
  • Experimental manipulation of OST subunit expression (overexpression and knockdown).
  • Assays to monitor ERAD of various misfolded proteins (type I/II membrane proteins and soluble glycoproteins).
  • Molecular dynamics simulations.

    • Main Results:

    • OST subunits were identified as key interactors with misfolded ER proteins during proteasomal inhibition.
    • Modulating OST subunit levels (overexpression or knockdown) significantly impacted ERAD efficiency for both glycosylated and non-glycosylated proteins, independent of glycosylation levels.
    • OST subunits were found to interact with the E3 ligase HRD1 and facilitate the retrotranslocation step of ERAD.
    • Molecular dynamics simulations suggested that OST transmembrane domains may thin the ER membrane, potentially aiding retrotranslocation.

    Conclusions:

    • The OST complex plays an unexpected, dual role in the ER, participating not only in N-glycosylation but also in the quality control and degradation of misfolded proteins via ERAD.
    • OST subunits are involved in the later stages of ERAD, interacting with HRD1 and potentially facilitating protein retrotranslocation through membrane distortion.
    retrotranslocation