title: N-linked sugar-regulated protein folding and quality control in the ER.
abstract: Asparagine-linked glycans (N-glycans) are displayed on the majority of proteins synthesized in the endoplasmic reticulum (ER). Removal of the outermost glucose residue recruits the lectin chaperone malectin possibly involved in a first triage of defective polypeptides. Removal of a second glucose promotes engagement of folding and quality control machineries built around the ER lectin chaperones calnexin (CNX) and calreticulin (CRT) and including oxidoreductases and peptidyl-prolyl isomerases. Deprivation of the last glucose residue dictates the release of N-glycosylated polypeptides from the lectin chaperones. Correctly folded proteins are authorized to leave the ER. Non-native polypeptides are recognized by the ER quality control key player UDP-glucose glycoprotein glucosyltransferase 1 (UGT1), re-glucosylated and re-addressed to the CNX/CRT chaperone binding cycle to provide additional opportunity for the protein to fold in the ER. Failure to attain the native structure determines the selection of the misfolded polypeptides for proteasome-mediated degradation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Abla
authors.initials: A
authors.lastname: Tannous
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.
authors.forename: Giorgia Brambilla
authors.initials: GB
authors.lastname: Pisoni
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003, USA. Electronic address: dhebert@biochem.umass.edu.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Hebert
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland; Institute for Research in Biomedicine, Protein Folding and Quality Control, CH-6500 Bellinzona, Switzerland; Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, CH-1015 Lausanne, Switzerland. Electronic address: maurizio.molinari@irb.usi.ch.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Molinari
mesh_terms: D000818:Animals; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011134:Polysaccharides / Q000378:metabolism*; D017510:Protein Folding
chemical_list: D037282:Calreticulin; D006023:Glycoproteins; D011134:Polysaccharides; D037281:Calnexin
keywords: Calnexin; Calreticulin; Endoplasmic reticulum; N-glycosylation; Protein folding and quality control; UDP-glucose glycoprotein glucosyltransferase 1