title: ER-golgi traffic is a prerequisite for efficient ER degradation.
abstract: Protein quality control is an essential function of the endoplasmic reticulum. Misfolded proteins unable to acquire their native conformation are retained in the endoplasmic reticulum, retro-translocated back into the cytosol, and degraded via the ubiquitin-proteasome system. We show that efficient degradation of soluble malfolded proteins in yeast requires a fully competent early secretory pathway. Mutations in proteins essential for ER-Golgi protein traffic severely inhibit ER degradation of the model substrate CPY*. We found ER localization of CPY* in WT cells, but no other specific organelle for ER degradation could be identified by electron microscopy studies. Because CPY* is degraded in COPI coat mutants, only a minor fraction of CPY* or of a proteinaceous factor required for degradation seems to enter the recycling pathway between ER and Golgi. Therefore, we propose that the disorganized structure of the ER and/or the mislocalization of Kar2p, observed in early secretory mutants, is responsible for the reduction in CPY* degradation. Further, we observed that mutations in proteins directly involved in degradation of malfolded proteins (Der1p, Der3/Hrd1p, and Hrd3p) lead to morphological changes of the endoplasmic reticulum and the Golgi, escape of CPY* into the secretory pathway and a slower maturation rate of wild-type CPY.
authors.affiliation: Institut für Biochemie, Universität Stuttgart, 70569 Stuttgart, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Taxis
authors.forename: Frank
authors.initials: F
authors.lastname: Vogel
authors.forename: Dieter H
authors.initials: DH
authors.lastname: Wolf
mesh_terms: D003513:Cycloheximide / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005838:Genotype; D006056:Golgi Apparatus / Q000502:physiology*; D007700:Kinetics; D010957:Plasmids; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D003513:Cycloheximide