Ras is involved in nerve-activity-dependent regulation of muscle genes.
Gene expression in skeletal muscle is regulated by the firing pattern of motor neurons, but the signalling systems involved in excitation-transcription coupling are unknown. Here, using in vivo transfection in regenerating muscle, we show that constitutively active Ras and a Ras mutant that selectively activates the MAPK(ERK) pathway are able to mimic the effects of slow motor neurons on expression of myosin genes. Conversely, the effect of slow motor neurons is inhibited by a dominant-negative Ras mutant. MAPK(ERK) activity is increased by innervation and by low-frequency electrical stimulation. These results indicate that Ras-MAPK signalling is involved in promoting nerve-activity-dependent differentiation of slow muscle fibres in vivo.
Murgia
M
M
Department of Biomedical Sciences and CNR Center of Muscle Biology and Physiopathology, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Serrano
A L
AL
Calabria
E
E
Pallafacchina
G
G
Lomo
T
T
Schiaffino
S
S
D019943:Amino Acid Substitution; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003714:Denervation; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005799:Genes, Dominant; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009046:Motor Neurons / Q000502:physiology; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development / Q000294:innervation / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D018631:ras Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D020929:Mitogen-Activated Protein Kinase Kinases; D018995:Myosin Heavy Chains; D018631:ras Proteins; D002045:Bupivacaine