Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of folding-defective glycoproteins.
Proteins synthesized in the endoplasmic reticulum (ER) lumen are exposed to several dedicated chaperones and folding factors that ensure efficient maturation. Nevertheless, protein folding remains error-prone and mutations in the polypeptide sequence may significantly reduce folding-efficiency. Folding-incompetent proteins carrying N-glycans are extracted from futile folding cycles in the calnexin chaperone system upon intervention of EDEM1, EDEM2 and EDEM3, three ER-stress-induced members of the glycosyl hydrolase 47 family. This review describes current knowledge about mechanisms regulating folding and disposal of glycoproteins.
Olivari
Silvia
S
Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland. silvia.olivari@irb.unisi.ch
Molinari
Maurizio
M
D000818:Animals; D002135:Calcium-Binding Proteins; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D017510:Protein Folding; D043323:alpha-Mannosidase / Q000378:metabolism
D002135:Calcium-Binding Proteins; C434526:Edem1 protein, mouse; D006023:Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C497155:EDEM2 protein, human; C510458:EDEM3 protein, mouse; D043323:alpha-Mannosidase