title: CaM kinase II-dependent phosphorylation of myogenin contributes to activity-dependent suppression of nAChR gene expression in developing rat myotubes.
abstract: During development of the neuromuscular junction (NMJ), extrajunctional expression of genes, whose products are destined for the synapse, is suppressed by muscle activity. One of the best-studied examples of activity-dependent gene regulation in muscle are those encoding nicotinic acetylcholine receptor (nAChR) subunits. We recently showed that nAChR gene expression is inhibited by calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKII inhibitors block activity-dependent suppression of these genes. Here we report results investigating the mechanism by which CaMKII suppresses nAChR gene expression. We show that the muscle helix-loop-helix transcription factor, myogenin, is necessary for activity-dependent control of nAChR gene expression in cultured rat myotubes and is a substrate for CaMKII both in vitro and in vivo. CaMKII phosphorylation of myogenin is induced by muscle activity and this phosphorylation influences DNA binding and transactivation. Thus we have identified a signaling mechanism by which muscle activity controls nAChR gene expression in developing muscle.
authors.affiliation: Mental Health Research Institute and the Department of Biological Chemistry, University of Michigan 205 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
authors.forename: Huibin
authors.initials: H
authors.lastname: Tang
authors.forename: Peter
authors.initials: P
authors.lastname: Macpherson
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Argetsinger
authors.forename: Danuta
authors.initials: D
authors.lastname: Cieslak
authors.forename: Steven T
authors.initials: ST
authors.lastname: Suhr
authors.forename: Christin
authors.initials: C
authors.lastname: Carter-Su
authors.forename: Daniel
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000201:enzymology; D018008:Myogenin / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000196:embryology* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; C503803:Myog protein, rat; D018008:Myogenin; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D008156:Luciferases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases