GSBS Student Publications
Title
A cell-based reglucosylation assay demonstrates the role of GT1 in the quality control of a maturing glycoprotein
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Biochemistry
Date
4-23-2008
Document Type
Article
Medical Subject Headings
Animals; CHO Cells; Cricetinae; Cricetulus; Glucose; Glycoproteins; Glycosylation; Hemagglutinins; Kinetics; Plasmids; Polysaccharides; Transcription, Genetic; Transfection; Transferases (Other Substituted Phosphate Groups)
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
The endoplasmic reticulum (ER) protein GT1 (UDP-glucose: glycoprotein glucosyltransferase) is the central enzyme that modifies N-linked carbohydrates based upon the properties of the polypeptide backbone of the maturing substrate. GT1 adds glucose residues to nonglucosylated proteins that fail the quality control test, supporting ER retention through persistent binding to the lectin chaperones calnexin and calreticulin. How GT1 functions in its native environment on a maturing substrate is poorly understood. We analyzed the reglucosylation of a maturing model glycoprotein, influenza hemagglutinin (HA), in the intact mammalian ER. GT1 reglucosylated N-linked glycans in the slow-folding stem domain of HA once the nascent chain was released from the ribosome. Maturation mutants that disrupted the oxidation or oligomerization of HA also supported region-specific reglucosylation by GT1. Therefore, GT1 acts as an ER quality control sensor by posttranslationally reglucosylating glycans on slow-folding or nonnative domains to recruit chaperones specifically to critical aberrant regions.
Rights and Permissions
Citation: J Cell Biol. 2008 Apr 21;181(2):309-20. Link to article on publisher's site
DOI of Published Version
10.1083/jcb.200712068
Related Resources
Journal Title
The Journal of cell biology
PubMed ID
18426978
Repository Citation
Pearse, Bradley R.; Gabriel, Luke; Wang, Ning; and Hebert, Daniel N., "A cell-based reglucosylation assay demonstrates the role of GT1 in the quality control of a maturing glycoprotein" (2008). GSBS Student Publications. 1488.
https://escholarship.umassmed.edu/gsbs_sp/1488