Effect of glycosylation inhibitors and acidotropic amines on the synthesis, processing, and intracellular-extracellular distribution of alpha-L-fucosidase in B-lymphoblastoid cells.
N-Methyldeoxynojirimycin, 1-deoxymannojirimycin, and monensin interferred with normal processing of asparagine-linked oligosaccharide chains of alpha-L-fucosidase in lymphoid cells by blocking conversion of high-mannose oligosaccharides of newly made precursor enzyme to complex oligosaccharides of mature intracellular and extracellular forms of enzyme. These compounds did not substantially alter the distribution of newly made alpha-L-fucosidase between intracellular and extracellular compartments. Thus, sorting of newly made alpha-L-fucosidase molecules that are retained intracellularly from molecules that are eventually secreted does not require terminal glycosylation or the trimming of glucose or alpha-D-(1----2)-linked mannose residues from carbohydrate chains. Chloroquine and ammonium chloride had no substantial effect on the structural processing or on the intracellular-extracellular distribution of alpha-L-fucosidase in lymphoid cells. In other cell types, these weak bases caused a massive secretion and an intracellular deficiency of acid hydrolases. The different responses to weak bases in lymphoid cells and the other cell types can be explained either by an inability of these agents to neutralize the pH of intracellular organelles in lymphoid cells or by a routing mechanism in lymphoid cells that is independent of pH.
DiCioccio
R A
RA
Department of Gynecologic Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263.
Mahoney
C M
CM
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000643:Ammonium Chloride / Q000494:pharmacology; D001402:B-Lymphocytes / Q000201:enzymology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006031:Glycosylation; D006801:Humans; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008985:Monensin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D005644:alpha-L-Fucosidase / Q000096:biosynthesis / Q000378:metabolism*
D000643:Ammonium Chloride; D014415:Tunicamycin; D017485:1-Deoxynojirimycin; D002738:Chloroquine; D008985:Monensin; D005959:Glucosidases; D008361:Mannosidases; D005644:alpha-L-Fucosidase; D005944:Glucosamine; C033424:N-methyldeoxynojirimycin