Protein kinase C and calcium/calmodulin-activated protein kinase II (CaMK II) suppress nicotinic acetylcholine receptor gene expression in mammalian muscle. A specific role for CaMK II in activity-dependent gene expression.
Nicotinic acetylcholine receptor (nAChR) gene expression is regulated by both muscle activity and increased intracellular calcium. This regulation is an important developmental event that rids receptors from the extrajunctional region of the developing muscle fiber. In avian muscle, it has been proposed that muscle activity suppresses nAChR gene expression via calcium-activated protein kinase C (PKC)-dependent phosphorylation of the myogenic transcription factor, myogenin. Here, we examined the role that PKC and other kinases play in mediating calcium- and activity-dependent suppression of nAChR genes in rat primary myotubes. We found that although activated PKC could regulate nAChR promoter activity and transiently suppressed both nAChR and myogenin gene expression, it did not appear to be required for calcium- or activity-dependent control of nAChR gene expression in mammalian muscle. Neither depletion of PKC from myotubes nor specific pharmacological inhibition of PKC blocked the suppression of nAChR gene expression produced by calcium or muscle depolarization. In contrast, we provide evidence that calcium/calmodulin-activated protein kinase II participates in mediating the effects of muscle depolarization on nAChR and myogenin gene expression.
Macpherson
Peter
P
Mental Health Research Institute and the Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Kostrominova
Tatiana
T
Tang
Huibin
H
Goldman
Daniel
D
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors; D018482:Muscle, Skeletal / Q000502:physiology*; D018008:Myogenin / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D013489:Suppression, Genetic; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection
C503803:Myog protein, rat; D018008:Myogenin; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D012433:Ryanodine; D000001:Calcimycin; D013779:Tetrodotoxin; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium