Reduced expression of the oligosaccharyltransferase exacerbates protein hypoglycosylation in cells lacking the fully assembled oligosaccharide donor

Glycobiology
Shiteshu Shrimal, Reid Gilmore

Abstract

A defect in the assembly of the oligosaccharide donor (Dol-PP-GlcNAc(2)Man(9)Glc(3)) for N-linked glycosylation causes hypoglycosylation of proteins by the oligosaccharyltransferase (OST). Mammalian cells express two OST complexes that have different catalytic subunits (STT3A or STT3B). We monitored glycosylation of proteins in asparagine-linked glycosylation 6 (ALG6) deficient cell lines that assemble Dol-PP-GlcNAc(2)Man(9) as the largest oligosaccharide donor. Based upon pulse labeling experiments, 30-40% of STT3A-dependent glycosylation sites and 20% of STT3B-dependent sites are skipped in ALG6-congenital disorders of glycosylation fibroblasts supporting previous evidence that the STT3B complex has a relaxed preference for the fully assembled oligosaccharide donor. Glycosylation of STT3B-dependent sites was more severely reduced in the ALG6 deficient MI8-5 cell line. Protein immunoblot analysis and RT-PCR revealed that MI8-5 cells express 2-fold lower levels of STT3B than the parental Chinese hamster ovary cells. The combination of reduced expression of STT3B and the lack of the optimal Dol-PP-GlcNAc(2)Man(9)Glc(3) donor synergize to cause very severe hypoglycosylation of proteins in MI8-5 cells. Thus, differences in OST sub...Continue Reading

References

Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·I StagljarM Aebi
Jan 8, 1999·Biochimica Et Biophysica Acta·P Burda, M Aebi
Feb 20, 1999·Journal of Cellular Biochemistry·J L O'RearS S Krag
Jul 29, 2000·Human Genetics·T ImbachT Hennet
Apr 18, 2001·Trends in Cell Biology·M Aebi, T Hennet
Jul 12, 2003·Molecular Genetics and Metabolism·J W NewellH H Freeze
Dec 18, 2004·Mutation Research·Martin Schröder, Randal J Kaufman
Jan 11, 2005·Molecular Genetics and Metabolism·Erik A EklundHudson H Freeze
Sep 13, 2005·Current Opinion in Structural Biology·Hudson H Freeze, Markus Aebi
May 6, 2008·American Journal of Human Genetics·Florence MolinariLaurence Colleaux
May 26, 2010·The Journal of Cell Biology·Bradley R PearseDaniel N Hebert
Jan 24, 2012·Journal of Cell Science·Peristera Roboti, Stephen High
Mar 27, 2013·The Journal of Cell Biology·Shiteshu ShrimalReid Gilmore
Apr 16, 2013·Biochimica Et Biophysica Acta·Markus Aebi
Jul 12, 2013·Human Molecular Genetics·Shiteshu ShrimalHudson H Freeze
Oct 10, 2013·Journal of Cell Science·Shiteshu Shrimal, Reid Gilmore
Aug 20, 2014·The Journal of Cell Biology·Natalia A CherepanovaReid Gilmore

❮ Previous
Next ❯

Citations

Jul 16, 2015·Expert Opinion on Biological Therapy·Martina Dicker, Richard Strasser
Apr 18, 2016·Current Opinion in Cell Biology·Natalia CherepanovaReid Gilmore
Apr 21, 2017·Journal of Child Neurology·Arunabha GhoshJill Clayton-Smith
Sep 2, 2017·The Journal of Cell Biology·Shiteshu ShrimalReid Gilmore
Apr 28, 2018·International Journal of Molecular Sciences·Sandra BrasilVanessa Dos Reis Ferreira
May 28, 2019·Endocrinology·George R Bousfield, David J Harvey

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.