Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle.
The mechanisms that determine how folding attempts are interrupted to target folding-incompetent proteins for endoplasmic reticulum-associated degradation (ERAD) are poorly defined. Here the alpha-mannosidase I-like protein EDEM was shown to extract misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. EDEM overexpression resulted in faster release of folding-incompetent proteins from the calnexin cycle and earlier onset of degradation, whereas EDEM down-regulation prolonged folding attempts and delayed ERAD. Up-regulation of EDEM during ER stress may promote cell recovery by clearing the calnexin cycle and by accelerating ERAD of terminally misfolded polypeptides.
Molinari
Maurizio
M
Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland. Maurizio.molinari@irb.unisi.ch
Calanca
Verena
V
Galli
Carmela
C
Lucca
Paola
P
Paganetti
Paolo
P
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D037281:Calnexin / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D008970:Molecular Weight; D011134:Polysaccharides / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D034622:RNA Interference; D014162:Transfection; D015854:Up-Regulation
C486654:EDEM1 protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D011134:Polysaccharides; D037281:Calnexin; D016282:Aspartic Acid Endopeptidases