Related Experiment Videos
Ras is involved in nerve-activity-dependent regulation of muscle genes
M Murgia1, A L Serrano, E Calabria
1Department of Biomedical Sciences and CNR Center of Muscle Biology and Physiopathology, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.
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.
Insights
Ras-MAPK signaling pathways regulate gene expression in skeletal muscle. This study reveals their crucial role in nerve-activity-dependent slow muscle fiber differentiation in vivo.
Area of Science:
- Molecular Biology
- Neuroscience
- Muscle Physiology
Background:
- Gene expression in skeletal muscle is influenced by motor neuron firing patterns.
- The specific signaling pathways mediating excitation-transcription coupling remain largely unknown.
Purpose of the Study:
- To investigate the role of Ras-MAPK signaling in mediating the effects of motor neuron activity on skeletal muscle gene expression.
- To elucidate the signaling mechanisms underlying nerve-activity-dependent differentiation of slow muscle fibers.
Main Methods:
- In vivo transfection in regenerating skeletal muscle.
- Utilizing constitutively active and dominant-negative Ras mutants.
- Measuring myosin gene expression and Mitogen-Activated Protein Kinase (ERK) pathway activity.
Main Results:
- Constitutively active Ras and Ras mutants activating the MAPK(ERK) pathway mimicked slow motor neuron effects on myosin gene expression.
- Dominant-negative Ras mutants inhibited the effects of slow motor neurons.
- Innervation and low-frequency electrical stimulation increased MAPK(ERK) activity.
Conclusions:
- Ras-MAPK signaling is essential for excitation-transcription coupling in skeletal muscle.
- This pathway mediates nerve-activity-dependent differentiation of slow muscle fibers in vivo.