Quality control of glycoprotein folding and ERAD: the role of N-glycan handling, EDEM1 and OS-9.
Protein N-glycosylation and quality control of protein folding as well as the connected ER-associated degradation of misfolded glycoproteins (ERAD) are not only evolutionary highly conserved but also functionally linked. It is now established that particular N-glycan structures which result from processing reactions by exo-glycosidases in the ER are of importance for glycoprotein folding and for ERAD. Thus, mono-glucosylated N-glycan intermediates harbor structural information which is important for promoting glycoprotein folding. On the other hand, specific mannose-trimmed N-glycans harbor structural information for routing misfolded glycoproteins to ERAD. In this review, we summarize current knowledge concerning the role played by glucosidases I and II, in concert with the bifunctional glucosyltransferase and calnexin/calreticulin in glycoprotein folding, the role of conventional ER mannosidase I in concert with the mannosidase EDEM1 in handling and routing of misfolded glycoproteins, and how the bifunctional OS-9 provides a link to the ER dislocon for degradation.
Division of Cell and Molecular Pathology, University of Zurich, 8091, Zurich, Switzerland. jurgen.roth@bluewin.ch.
Jürgen
http://orcid.org/0000-0001-7449-0450
J
Roth
Division of Cell and Molecular Pathology, University of Zurich, 8091, Zurich, Switzerland.
Christian
C
Zuber
D060746:Endoplasmic Reticulum-Associated Degradation; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D011786:Quality Control
C486654:EDEM1 protein, human; D006023:Glycoproteins; D037102:Lectins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C098898:OS9 protein, human; D011134:Polysaccharides
EDEM1; ER mannosidase I; ERAD; Endoplasmic reticulum; Glucosidase I; Glucosidase II; Glucosyltransferase; OS-9; Protein N-glycosylation; Protein folding