Effect of tunicamycin, an inhibitor of protein glycosylation, on the biological properties of acetylcholine receptor in cultured muscle cells.
We have studied the effect of tunicamycin (TM), an antibiotic which inhibits the glycosylation of nascent proteins, on the properties of the acetylcholine receptor (AChR) at the surface of embryonic chick skeletal muscle cells. The use of two separate assays, specific binding of 125I-alpha-bungarotoxin and carbamylcholine-activated 22Na+ uptake, has allowed us to monitor the effects of impaired glycosylation on the metabolic and functional properties of AChR. A significant decrease in the amounts of surface AChR elaborated in the presence of TM is detected by both measurements. This decrease has been found to reflect an enhanced proteolytic degradation of the underglycosylated AChR. The underglycosylated AChR, expressed on the cell surface in the presence of TM, retains the capability of mediating agonist-activated ionic permeability changes, but displays quantitatively altered interactions with receptor ligands. We conclude that the carbohydrate moiety on AChR may play a role in determining the folding of newly synthesized polypeptides to form a conformation compatible with the metabolic properties and ligand interactions characteristic of glycosylated AChR.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003208:Concanavalin A / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives*; D007700:Kinetics; D009132:Muscles / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
D011950:Receptors, Cholinergic; D003208:Concanavalin A; D014415:Tunicamycin; D002217:Carbachol; D003513:Cycloheximide; D012964:Sodium; D005944:Glucosamine