Substrate-Specific Requirements for UGT1-Dependent Release from Calnexin

Soldà, Tatiana; Galli, Carmela; Kaufman, Randal J.; Molinari, Maurizio

doi:10.1016/j.molcel.2007.05.032

Cited by 81 publications

(79 citation statements)

References 46 publications

(65 reference statements)

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“…Trimming of the innermost glucose residue by glucosidase II releases those polypeptides from CNX/CRT. UDP-glucose/glycoprotein glucosyl transferase (UGGT) senses the folding state of released glycoproteins and, if the correct conformation has not been achieved, UGGT reglucosylates the N-glycan again to be reengaged by CNX/CRT (Solda et al 2007;D'Alessio et al 2010). In this way, the structure of the N-glycan codes the mandatory information for folding state of the glycoproteins (Hebert et al 2005;Aebi et al 2010).…”

Section: Protein Folding and Posttranslational Modification Glycosylamentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

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The endoplasmic reticulum (ER) uses an elaborate surveillance system called the ER quality control (ERQC) system. The ERQC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded polypeptides through ER-associated degradation (ERAD) or autophagic degradation. This mechanism of ER protein surveillance is closely linked to redox and calcium homeostasis in the ER, whose balance is presumed to be regulated by a specific cellular compartment. The potential to modulate proteostasis and metabolism with chemical compounds or targeted siRNAs may offer an ideal option for the treatment of disease.

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Section: Protein Folding and Posttranslational Modification Glycosylamentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

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“…of Biochemistry, University of Alberta, USA). MEF UGT1d (Solda et al, 2007) were a gift from Tatiana Soldà (Institute for Research in Biomedicine, Protein Folding and Quality Control, Switzerland Università della Svizzera Italiana, Switzerland). Cells were grown at 37°C and 5% CO 2 in high-glucose (4.5 g/l) Dulbecco's modified Eagle's medium (DMEM) medium (GE Healthcare) supplemented with 10% FCS (Biochrom, Berlin, Germany), 2 mM glutamine, 100 U/ml penicillin and 100 µg/ml streptomycin.…”

Section: Cellsmentioning

confidence: 99%

The murine cytomegalovirus immunoevasin gp40 binds MHC class I molecules to retain them in the early secretory pathway

Janssen

Ramnarayan

Abo-Elmagd

et al. 2016

Journal of Cell Science

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In the presence of the murine cytomegalovirus (mCMV) gp40 (m152) protein, murine major histocompatibility complex (MHC) class I molecules do not reach the cell surface but are retained in an early compartment of the secretory pathway. We find that gp40 does not impair the folding or high-affinity peptide binding of the class I molecules but binds to them, leading to their retention in the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, most likely by retrieval from the cis-Golgi to the ER. We identify a sequence in gp40 that is required for both its own retention in the early secretory pathway and for that of class I molecules.

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“…According to their rates of release from CNX/CRT association, glycoproteins expressed in fibroblasts derived from GT-minus mouse embryos could be classified in three classes; in the first one, the observed rates were similar to those in wildtype cells (18). Glycoproteins in this class represent those with only one cycle of association with the lectins triggered by partial deglucosylation of the transferred glycan.…”

Section: What Happens Once Glycoproteins Are In Cnx/crt Cycles?mentioning

confidence: 99%

“…The most intriguing case was that of glycoproteins in the third class, as they showed a prolonged association with CNX/CRT. It was speculated that the observed results could be due to a protein-protein association between the lectins and glycoproteins or, alternatively, to the fact that a selenocysteine-containing oxidoreductase (Sep15) that forms a 1:1 complex with GT could play a role in assessing and refining the disulfide bond content of glycoproteins in this class (18,19).…”

Section: What Happens Once Glycoproteins Are In Cnx/crt Cycles?mentioning

confidence: 99%

Getting In and Out from Calnexin/Calreticulin Cycles

Caramelo

Parodi

2008

Journal of Biological Chemistry

269

229

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The N-glycan-dependent quality control mechanism of glycoprotein folding was proposed initially by Helenius and coworkers several years ago; with a few minor modifications, it is still valid today ( Fig. 1) (1-3).2 Glycan processing starts immediately after its transfer from a dolichol-P-P derivative to Asn residues in nascent polypeptide chains entering the lumen of the ER. 3 Removal of the outermost and following glucoses by the successive action of GI and GII exposes the Glc 1 Man 9 GlcNAc 2 epitope (Fig. 2). This structure is then recognized by two ER resident lectins (CNX and CRT) that specifically bind monoglucosylated polymannose glycans. This is followed by removal of the innermost glucose by GII, thus liberating the glycoprotein from the lectin anchor. The proteinlinked glycan is then reglucosylated by the soluble ER enzyme GT only if the protein moiety displays non-native three-dimensional structures, as this enzyme behaves as a conformational sensor. Cycles of CNX/CRT-glycoprotein binding and liberation, catalyzed by the opposing activities of GT and GII, are terminated once glycoproteins attain their native structures. Glucose-free glycoproteins then continue their transit through the secretory pathway. Alternatively, permanently misfolded glycoproteins may be then transported to the cytosol for proteasomal degradation. Lectin-glycoprotein association not only thwarts Golgi exit of folding intermediates and irreparably misfolded glycoproteins but also enhances folding efficiency by preventing aggregation and promoting proper disulfide bonding. The latter is catalyzed by an oxidoreductase of the proteindisulfide isomerase family (ERp57) that acts exclusively on glycoproteins, as it is loosely associated with CNX/CRT.GT is the only component of the quality control mechanism that senses protein conformations, as it recognizes hydrophobic amino acid patches exposed in molten globule-like conformers (4, 5). GT may also glucosylate glycoproteins in not fully assembled oligomeric complexes because it also recognizes hydrophobic surfaces exposed as a consequence of the absence of subunit components (6). The aim of this review is to give an overview of recent reports dealing with the entrance and exit of glycoproteins from CNX/CRT cycles. Getting In: GII Is Not What It Was Thought to BeThe first step in the pathway leading to the entrance of glycoproteins into CNX/CRT cycles is the removal of the outermost glucose unit from the glycan by the membrane enzyme GI. This reaction occurs almost simultaneously with glycan transfer. The rapid GI-mediated deglucosylation of the protein-linked glycan, as well as the apparent inability of the enzyme to remove in vivo (but not in vitro) the glucose from the dolichol-P-P-linked glycan, strongly suggests the existence of a supercomplex formed by the oligosaccharyltransferase, GI, and the dolichol derivative, with a very precise orientation of the components.It was assumed that the sole role of GII was that of removing glucose residues l and n (Fig. 2). Recent work has sugg...

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Substrate-Specific Requirements for UGT1-Dependent Release from Calnexin

Cited by 81 publications

References 46 publications

Protein Folding and Quality Control in the ER

Protein Folding and Quality Control in the ER

The murine cytomegalovirus immunoevasin gp40 binds MHC class I molecules to retain them in the early secretory pathway

Getting In and Out from Calnexin/Calreticulin Cycles

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