CaM kinase II-dependent phosphorylation of myogenin contributes to activity-dependent suppression of nAChR gene expression in developing rat myotubes.
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.
Tang
Huibin
H
Mental Health Research Institute and the Department of Biological Chemistry, University of Michigan 205 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Macpherson
Peter
P
Argetsinger
Lawrence S
LS
Cieslak
Danuta
D
Suhr
Steven T
ST
Carter-Su
Christin
C
Goldman
Daniel
D
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
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