title: Reglucosylation by UDP-glucose:glycoprotein glucosyltransferase 1 delays glycoprotein secretion but not degradation.
abstract: UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1) is a central quality control gatekeeper in the mammalian endoplasmic reticulum (ER). The reglucosylation of glycoproteins supports their rebinding to the carbohydrate-binding ER molecular chaperones calnexin and calreticulin. A cell-based reglucosylation assay was used to investigate the role of UGT1 in ER protein surveillance or the quality control process. UGT1 was found to modify wild-type proteins or proteins that are expected to eventually traffic out of the ER through the secretory pathway. Trapping of reglucosylated wild-type substrates in their monoglucosylated state delayed their secretion. Whereas terminally misfolded substrates or off-pathway proteins were most efficiently reglucosylated by UGT1, the trapping of these mutant substrates in their reglucosylated or monoglucosylated state did not delay their degradation by the ER-associated degradation pathway. This indicated that monoglucosylated mutant proteins were actively extracted from the calnexin/calreticulin binding-reglucosylation cycle for degradation. Therefore trapping proteins in their monoglucosylated state was sufficient to delay their exit to the Golgi but had no effect on their rate of degradation, suggesting that the degradation selection process progressed in a dominant manner that was independent of reglucosylation and the glucose-containing A-branch on the substrate glycans.
authors.affiliation: Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003 Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003.
authors.forename: Abla
authors.initials: A
authors.lastname: Tannous
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003.
authors.forename: Nishant
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003.
authors.forename: Taku
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003 Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003 dhebert@biochem.umass.edu.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Hebert
mesh_terms: D000818:Animals; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation; D005964:Glucosyltransferases / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D017510:Protein Folding; D021381:Protein Transport
chemical_list: D037282:Calreticulin; D006023:Glycoproteins; D037281:Calnexin; D005964:Glucosyltransferases; C072423:mannosylglycoprotein 1,3-glucosyltransferase