Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Animals
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Bupivacaine / pharmacology
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Cell Division / drug effects
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Denervation
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Electric Stimulation
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Genes, Dominant
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology
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Male
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Motor Neurons / physiology
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Muscle Development
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / growth & development
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Muscle, Skeletal / innervation
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Muscle, Skeletal / metabolism*
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Mutagenesis, Site-Directed
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Myosin Heavy Chains / biosynthesis
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Plasmids / genetics
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Rats
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Rats, Wistar
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Regeneration / drug effects
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Regeneration / physiology
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Signal Transduction / drug effects
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Signal Transduction / genetics
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ras Proteins / biosynthesis*
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ras Proteins / genetics
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ras Proteins / pharmacology
Substances
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Mitogen-Activated Protein Kinase Kinases
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Myosin Heavy Chains
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ras Proteins
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Bupivacaine