cAMP stimulation of acetylcholine receptor expression is mediated through posttranslational mechanisms.
When the four Torpedo acetylcholine receptor (AcChoR) subunit cDNAs are stably integrated into the genome of mouse fibroblast cells, alpha 2 beta gamma delta pentamers with proper pharmacological and electrophysiological properties are expressed on the cell surface. Expression of these AcChoRs can be regulated by agents that stimulate intracellular cAMP levels with the result that increased numbers of cell-surface AcChoRs are produced. Theophylline, 8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate, cholera toxin, and forskolin stimulated AcChoR cell-surface expression 1.2-, 1.6-, 2.2-, and 2.3-fold, respectively. cAMP-stimulated expression is mediated through a posttranslational mechanism, and the observed increase in surface AcChoRs correlates with increased lifetimes of each newly synthesized subunit. Increased subunit lifetimes are not observed in cell lines expressing each subunit individually, indicating that subunit stabilization arises through heterologous subunit-subunit interactions.
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Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510.
Ross
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Claudio
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D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D007700:Kinetics; D007739:L Cells / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000235:genetics*; D013806:Theophylline / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*; D014101:Torpedo; D014162:Transfection
D002038:Bungarotoxins; D046911:Macromolecular Substances; D011950:Receptors, Cholinergic; D013873:Thionucleotides; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D004247:DNA; D002772:Cholera Toxin; D003513:Cycloheximide; D013806:Theophylline; D000242:Cyclic AMP