title: Protein O-mannosyltransferases participate in ER protein quality control.
abstract: In eukaryotic cells, proteins enter the secretory pathway at the endoplasmic reticulum (ER) as linear polypeptides and fold after translocation across or insertion into the membrane. If correct folding fails, many proteins are O-mannosylated inside the ER by an O-mannosyltransferase, the Pmt1p-Pmt2p complex. The consequences of this modification are controversial and the cellular role of the Pmt1p-Pmt2p complex in this respect is unclear. Here, we have identified the binding partners of yeast Pmt1p and Pmt2p. These include ER chaperones involved in oxidative protein folding; the Hrd1p complex, which is involved in ER-associated protein degradation (ERAD); and the p24 protein complex involved in ER export. The results suggest that the Pmt1p-Pmt2p complex participates in these processes. We tested this assumption in a functional assay and found that whereas the Pmt1p-Pmt2p complex promotes fast ER export of the GPI-anchored protein Gas1p, it retains the misfolded version Gas1*p and targets it to the Hrd1p complex for subsequent degradation. Our results reveal previously unknown cellular roles of the Pmt1p-Pmt2p complex in connection with the ERAD machinery and show its participation in ER protein quality control.
authors.affiliation: Department of Genetics, University of Seville, Ave Reina Mercedes 6, 41012 Seville, Spain. vgoder@us.es
authors.forename: Veit
authors.initials: V
authors.lastname: Goder
authors.forename: Alejandro
authors.initials: A
authors.lastname: Melero
mesh_terms: D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: C066709:GAS1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; C104621:HRD1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase