title: Induction of a storage phenotype and abnormal intracellular localization of apical glycoproteins are two independent responses to GalNAcalpha-O-bn.
abstract: Our previous studies on an inhibitor of O-glycosylation of glycoproteins, GalNAcalpha-O-bn, in the model of enterocytic HT-29 cells, have shown at the cellular level an alteration of the normal localization of apical glycoproteins, and at the biochemical level an in situ synthesis and storage of sialylated GalNAcalpha-O-bn oligosaccharides. The purpose of this study was to examine if a relation existed between these two events, using different cell lines. Intracellular storage of GalNAcalpha-O-bn metabolites occurred in HT-29 and CAPAN-1 cells but not in Caco-2 cells. On the other hand, an accumulation of endosomal/lysosomal compartments was observed in HT-29 and CAPAN-1 cells but not in Caco-2 cells. These data focused on a GalNAcalpha-O-bn-derived storage phenotype in HT-29 and CAPAN-1 cells. The apical membrane glycoproteins MUC1 and CEA showed an abnormal localization inside intracytoplasmic vesicles in HT-29 cells, whereas they kept their normal localization in Caco-2 and CAPAN-1 cells. Studies on the glycosylation of these apical glycoproteins showed that GalNAcalpha-O-bn inhibited the glycosylation in a cell-specific manner. The alteration in the apical targeting of glycoproteins, and the appearance of a GalNAcalpha-O-bn-derived storage phenotype are two independent and cell type-specific events. The former depends on the inhibition pattern of the glycosylation of endogenous glycoproteins, whereas the latter is connected to the intracellular accumulation of GalNAcalpha-O-bn metabolites.
authors.affiliation: Unité INSERM 560 and Service d'Anatomie Pathologique, Lille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.forename: Valérie
authors.initials: V
authors.lastname: Gouyer
authors.forename: Delphine
authors.initials: D
authors.lastname: Delacour
authors.forename: Brigitte
authors.initials: B
authors.lastname: Hémon
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pons
authors.forename: Colette
authors.initials: C
authors.lastname: Richet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zanetta
authors.forename: Guillemette
authors.initials: G
authors.lastname: Huet
mesh_terms: D000941:Antigens / Q000378:metabolism; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D011992:Endosomes / Q000378:metabolism; D005690:Galactose / Q000031:analogs & derivatives / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D018396:Mucin-1; D009077:Mucins
chemical_list: C411946:1-benzyl-2-acetamido-2-galactopyranoside; D000941:Antigens; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D005690:Galactose