title: Different sorting of Lys-Asp-Glu-Leu proteins in rat liver.
abstract: Most of the resident soluble proteins of the endoplasmic reticulum (ER) seem to be sorted into this compartment via their COOH-terminal tetrapeptide Lys-Asp-Glu-Leu (KDEL). This sorting is supposed to occur in a post-ER compartment. Three resident soluble ER glycoproteins belonging to the KDEL family are CaBP1, CaBP2, CaBP3 (= calreticulin), and CaBP4 (= grp94) (Nguyen Van, P., Peter, F., and Söling, H.-D. (1989) J. Biol. Chem. 264, 17494-17501). In rat liver, calreticulin possesses a carbohydrate moiety of the complex hybrid type with terminal galactoses (Nguyen Van, P., Peter, F., and Söling, H.-D. (1989) J. Biol. Chem. 264, 17494-17501). We can show now that practically all calreticulin molecules (and not only a fraction) possess terminal galactoses as well as the COOH-terminal KDEL sequence. This as well as pulse-chase experiments performed at 37 and 15 degrees C indicate that calreticulin must have passed through the trans-Golgi. Subcellular fractionations of post-mitochondrial supernatants from isolated rat hepatocytes by sucrose-Nycodenz gradient centrifugation revealed that calreticulin is confined mainly to the rough ER, grp94 mainly to the smooth ER. CaBP1, a member of the thioredoxin family, was recovered in fractions which most likely represent the intermediate compartment. This indicates that KDEL is a sorting signal which leads to the retention of these proteins in the pre-Golgi compartments. However, additional factors, most likely residing within the specific KDEL protein itself, determine the final location of the protein within the pre-Golgi compartments. This is underlined by experiments in which the density dependent distribution of total KDEL proteins was studied using a COOH-terminal KDEL-specific antibody.
authors.affiliation: Abteilung Klinische Biochemie, Universität Göttingen, Federal Republic of Germany.
authors.forename: F
authors.initials: F
authors.lastname: Peter
authors.forename: P
authors.initials: P
authors.lastname: Nguyen Van
authors.forename: H D
authors.initials: HD
authors.lastname: Söling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D037282:Calreticulin; D016521:Electrophoresis, Gel, Pulsed-Field; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005692:Galactose Oxidase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D010504:Periodic Acid / Q000378:metabolism; D037121:Plant Lectins; D021382:Protein Sorting Signals; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D018000:Receptors, Peptide
chemical_list: D002135:Calcium-Binding Proteins; D037282:Calreticulin; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C064459:KDEL receptor; D037102:Lectins; D008565:Membrane Proteins; D009842:Oligopeptides; D037121:Plant Lectins; D021382:Protein Sorting Signals; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C018551:glucose-regulated proteins; C043696:jacalin; D010504:Periodic Acid; C073762:lysyl-aspartyl-glutamyl-leucine; C009288:metaperiodate; D005692:Galactose Oxidase; D005690:Galactose