title: Intracellular signaling molecules involved in an inhibitory factor-induced decrease in fetal-type AChR expression.
abstract: The innervation-induced down-regulation of fetal-type acetylcholine receptor (AChR) expression in developing muscle fibers has largely been attributed to nerve-evoked muscle activity; however, there is increasing evidence that a neural trophic factor also contributes to this receptor down-regulation. Previous studies from this laboratory have shown that neural extracts contain a factor which decreases fetal-type AChR expression in skeletal muscle cell lines and therefore may account for the proposed inhibitory neurotrophic influence. The current study investigated possible intracellular signaling molecules involved in this receptor down-regulation and demonstrated that activation of protein kinase C and p70(S6k) appeared to be important in receptor down-regulation. Decreases in AChR density were independent of myogenin. In addition, the receptor down-regulation was independent of neuregulin, which also induces p70(S6k) activity. These studies demonstrate that neural extracts contain an inhibitory factor which can down-regulate fetal-type AChR expression independently of nerve-evoked muscle activity through intracellular signaling molecules which are known to regulate AChR expression.
authors.affiliation: Department of Physiology, School of Medical Sciences, and Centre for Neurosciences, Otago University, PO Box 913, Dunedin, New Zealand.
authors.forename: J M
authors.initials: JM
authors.lastname: Montgomery
authors.forename: G
authors.initials: G
authors.lastname: Corfas
authors.forename: R G
authors.initials: RG
authors.lastname: Mills
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D003994:Bucladesine / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D002645:Chickens; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005326:Fetal Proteins / Q000096:biosynthesis*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D018008:Myogenin / Q000378:metabolism; D020880:Neuregulins / Q000037:antagonists & inhibitors / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011950:Receptors, Cholinergic / Q000096:biosynthesis*; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014020:Tissue Extracts / Q000494:pharmacology
chemical_list: D003994:Bucladesine; D002273:Carcinogens; D004791:Enzyme Inhibitors; D005326:Fetal Proteins; D018008:Myogenin; D020880:Neuregulins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D011950:Receptors, Cholinergic; D019893:Ribosomal Protein S6 Kinases; D013755:Tetradecanoylphorbol Acetate; D014020:Tissue Extracts; C503799:MYOG protein, human; C503801:Myog protein, mouse