CaM kinase II-dependent phosphorylation of myogenin contributes to activity-dependent suppression of nAChR gene expression in developing rat myotubes

Cell Signal. 2004 May;16(5):551-63. doi: 10.1016/j.cellsig.2003.09.006.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Luciferases / genetics
  • Luciferases / metabolism
  • Muscle Contraction / physiology
  • Muscle Development / physiology*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / enzymology
  • Myogenin / metabolism*
  • Neuromuscular Junction / embryology*
  • Neuromuscular Junction / enzymology*
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic
  • Rats
  • Receptors, Nicotinic / genetics*
  • Receptors, Nicotinic / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction / drug effects


  • Enzyme Inhibitors
  • Myog protein, rat
  • Myogenin
  • Receptors, Nicotinic
  • Recombinant Proteins
  • Luciferases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases