Oligosaccharyltransferase Is Involved in Targeting to ER-Associated Degradation
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Antibodies
2.3. Plasmids and Constructs
2.4. Cell Culture, Media and Transfections
2.5. BAP Construct Transfection and Probing
2.6. Metabolic Labeling
2.7. Immunoprecipitation, Crosslinking and Immunoblotting
2.8. Iodixanol Equilibrium Sedimentation Gradient
2.9. Immunofluorescence Microscopy
2.10. Proteomics
2.11. Bioinformatics Analysis
2.12. Statistical Analysis
3. Results
3.1. Identification of OST as ERAD Substrate Interactor by a SILAC Proteomics Approach
3.2. Shared Subcellular Localization and Increased Interaction of OST Subunits with the ERAD Substrate upon Proteasomal Inhibition
3.3. OST Subunits Promote the Degradation of Glycosylated H2a and to a Lesser Extent of Its Non-Glycosylated Mutant
3.4. OST Subunits Participate in ERAD of Other Membrane and Luminal Substrates
3.5. Interaction Between DAD1 and HRD1 and Promotion of Retrotranslocation by OST Subunits
3.6. Molecular Dynamics Simulation Suggest Membrane Thinning by OST
4. Discussion
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALLN | N-acetyl-Leu-Leu-norleucinal |
BACE476 | beta-secretase 1 mutant 476 |
BAP | biotin-acceptor peptide |
BirA | E. coli biotin ligase BirA |
Bz | Bortezomib |
CNX | Calnexin |
DAD1 | Defender Against apoptotic cell Death 1 |
ECL | enhanced chemiluminescence |
ER | endoplasmic reticulum |
ERAD | ER-associated degradation |
ERQC | ER-derived quality control compartment |
Fbs2 | Skp1-Cullin1-F-box protein 2 |
Herp | Homocysteine-inducible Endoplasmic Reticulum (ER) Stress Protein |
HRD1 | HMG-CoA Reductase Degradation Protein 1 |
H2a | uncleaved precursor of human asialoglycoprotein receptor H2a. Gene: ASGPR2 |
H2aΔgly | H2a mutated in its three glycosylation sites |
H2aSBP | H2aG78R uncleavable mutant fused through its C-terminus to a 38-amino acid streptavidin binding peptide |
Lac | Lactacystin |
NHK | human α1-antitrypsin variant null Hong Kong |
OS-9 | Amplified in Osteosarcoma 9 |
OST | oligosaccharyltransferase |
SEL1L | Suppressor of lin-12-like protein 1 |
SEP15 | Selenoprotein 15 or Selenof |
SERCA2 | Sarco(endo)plasmic reticulum calcium-ATPase 2 |
SILAC | stable isotope labeling by amino acids in cell culture |
STT3A | STT3 oligosaccharyltransferase complex catalytic subunit A |
STT3B | STT3 oligosaccharyltransferase complex catalytic subunit B |
TDP43 | TAR DNA-binding protein 43 |
TMD | transmembrane domain |
Tusc3 | tumor suppressor candidate 3 |
Tun | Tunicamycin |
Ubxd8 | ubiquitin regulatory X domain-containing protein 8 |
UGGT1 | UDP-glucose glycoprotein glucosyltransferase 1 |
XTP3-B | XTP3-transactivated gene B protein or ER lectin 1 |
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Shenkman, M.; Ogen-Shtern, N.; Patel, C.; Saad, H.; Groisman, B.; Pasmanik-Chor, M.; Schermann, S.M.; Körner, R.; Lederkremer, G.Z. Oligosaccharyltransferase Is Involved in Targeting to ER-Associated Degradation. Cells 2025, 14, 1593. https://doi.org/10.3390/cells14201593
Shenkman M, Ogen-Shtern N, Patel C, Saad H, Groisman B, Pasmanik-Chor M, Schermann SM, Körner R, Lederkremer GZ. Oligosaccharyltransferase Is Involved in Targeting to ER-Associated Degradation. Cells. 2025; 14(20):1593. https://doi.org/10.3390/cells14201593
Chicago/Turabian StyleShenkman, Marina, Navit Ogen-Shtern, Chaitanya Patel, Haddas Saad, Bella Groisman, Metsada Pasmanik-Chor, Sonya M. Schermann, Roman Körner, and Gerardo Z. Lederkremer. 2025. "Oligosaccharyltransferase Is Involved in Targeting to ER-Associated Degradation" Cells 14, no. 20: 1593. https://doi.org/10.3390/cells14201593
APA StyleShenkman, M., Ogen-Shtern, N., Patel, C., Saad, H., Groisman, B., Pasmanik-Chor, M., Schermann, S. M., Körner, R., & Lederkremer, G. Z. (2025). Oligosaccharyltransferase Is Involved in Targeting to ER-Associated Degradation. Cells, 14(20), 1593. https://doi.org/10.3390/cells14201593