| Persistent glycoprotein misfolding activates the glucosidase II/UGT1-driven calnexin cycle to delay aggregation and loss of folding competence. | |
MedLine Citation:
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PMID: 16307915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The UDP-glucose:glycoprotein glucosyltransferase (UGT) is a central player of glycoprotein quality control in the endoplasmic reticulum (ER). UGT reglucosylation of nonnative glycopolypeptides prevents their release from the calnexin cycle and secretion. Here, we compared the fate of a glycoprotein with a reversible, temperature-dependent folding defect in cells with and without UGT1. Upon persistent misfolding, tsO45 G was slowly released from calnexin and entered a second level of retention-based ER quality control by forming BiP/GRP78-associated disulfide-bonded aggregates. This correlated with loss in the ability to correct misfolding. Deletion of UGT1 did not affect the stringency of ER quality control. Rather, it accelerated release from calnexin and transfer to the second ER quality control level, but it did so after an unexpectedly long lag, showing that cycling in the calnexin chaperone system is not frenetic, as claimed by existing models, and is fully activated only upon persistent glycoprotein misfolding. |
Authors:
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Maurizio Molinari; Carmela Galli; Omar Vanoni; Stacey M Arnold; Randal J Kaufman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cell Volume: 20 ISSN: 1097-2765 ISO Abbreviation: Mol. Cell Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-11-25 Completed Date: 2006-01-05 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 503-12 Citation Subset: IM |
Affiliation:
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Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland. maurizio.molinari@irb.unisi.ch |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calnexin / metabolism* Cell Line Cystine / metabolism Endoplasmic Reticulum / enzymology, metabolism Gene Deletion Glucosyltransferases / genetics, physiology* Glycoproteins / chemistry*, metabolism*, physiology Glycosylation Hot Temperature Mice Protein Denaturation Protein Folding * Stem Cells / enzymology, metabolism alpha-Glucosidases / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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GM07767/GM/NIGMS NIH HHS; HL052173/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Glycoproteins; 139873-08-8/Calnexin; 56-89-3/Cystine; EC 2.4.1.-/Glucosyltransferases; EC 2.4.1.-/mannosylglycoprotein 1,3-glucosyltransferase; EC 3.2.1.-/4-nitrophenyl-alpha-glucosidase; EC 3.2.1.20/alpha-Glucosidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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