title: Degradation of endoplasmic reticulum (ER) quality control substrates requires transport between the ER and Golgi.
abstract: Endoplasmic reticulum (ER) quality control (ERQC) components retain and degrade misfolded proteins, and our results have found that the degradation of the soluble ERQC substrates CPY* and PrA* but not membrane spanning ERQC substrates requires transport between the ER and Golgi. Stabilization of these misfolded soluble proteins was seen in cells lacking Erv29p, a probable Golgi localized protein that cycles through the ER by means of a di-lysine ER retrieval motif (KKKIY). Cells lacking Erv29p also displayed severely retarded ER exit kinetics for a subset of correctly folded proteins. We suggest that Erv29p is likely involved in cargo loading of a subset of proteins, including soluble misfolded proteins, into vesicles for ER exit. The stabilization of soluble ERQC substrates in both erv29Delta cells and sec mutants blocked in either ER exit (sec12) or vesicle delivery to the Golgi (sec18) suggests that ER-Golgi transport is required for ERQC and reveals a new aspect of the degradative mechanism.
authors.affiliation: Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Caldwell
authors.forename: K J
authors.initials: KJ
authors.lastname: Hill
authors.forename: A A
authors.initials: AA
authors.lastname: Cooper
mesh_terms: D000595:Amino Acid Sequence; D002268:Carboxypeptidases / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology; D043402:Cathepsin A; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D017510:Protein Folding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; C432391:Erv29 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D002268:Carboxypeptidases; D043402:Cathepsin A