title: Lysosomal alpha-glucosidase: cell-specific processing and altered maturation in HT-29 colon cancer cells.
abstract: We have previously described the abnormal localization of resident Golgi proteins and O-glycans in the rough endoplasmic reticulum of mucin-secreting HT-29 M6 colon cancer cells, suggesting altered protein trafficking in these cells [Egea, Francí, Gambús, Lesuffleur, Zweibaum and Real (1993) J. Cell Sci. 105, 819-830]. In the present work, we have chosen lysosomal alpha-glucosidase as a reporter to examine the intracellular traffic of glycoproteins in M6 cells. We have compared the synthesis and processing of alpha-glucosidase in mucin-secreting M6 cells and in Caco-2 colon cancer cells, the latter resembling normal absorptive intestinal epithelium. Our results show that alpha-glucosidase processing and secretion is markedly delayed in M6 cells as compared to Caco-2 cells or normal fibroblasts, and this delay is caused by an accumulation of alpha-glucosidase precursor form in the trans-Golgi network. Furthermore, treatment in Caco-2 cells with brefeldin A led to changes in alpha-glucosidase maturation similar to those observed in untreated M6 cells. To determine whether altered processing occurs in other cultured cells, a panel of cancer cell lines and cultures from normal exocrine pancreas were examined. In pancreas-derived cultures, alpha-glucosidase showed a processing pattern different from that described until now. Only HT-29 cells and HT-29-derived subpopulations displayed a defect in alpha-glucosidase maturation. In conclusion, alpha-glucosidase processing is more diverse than has previously been described; this finding may have tissue-specific functional implications.
authors.affiliation: Departament d'Immunologia, Institut Municipal d'Investigació Mèdica, Universitat Autònoma de Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Francí
authors.forename: G
authors.initials: G
authors.lastname: Egea
authors.forename: R
authors.initials: R
authors.lastname: Arribas
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
authors.forename: F X
authors.initials: FX
authors.lastname: Real
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000641:Ammonia / Q000494:pharmacology; D020126:Brefeldin A; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology*; D003517:Cyclopentanes / Q000494:pharmacology; D011992:Endosomes / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000201:enzymology; D019073:HT29 Cells; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000201:enzymology* / Q000378:metabolism; D019158:N-Acetylneuraminic Acid; D010179:Pancreas / Q000201:enzymology; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D011480:Protease Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000378:metabolism; D013696:Temperature; D014407:Tumor Cells, Cultured; D000520:alpha-Glucosidases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D003517:Cyclopentanes; D011480:Protease Inhibitors; D012794:Sialic Acids; D020126:Brefeldin A; D000641:Ammonia; D006596:Hexosaminidases; D000520:alpha-Glucosidases; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D019158:N-Acetylneuraminic Acid