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Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways

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Abstract

Myostatin, a member of the transforming growth factor-β superfamily, is a potent negative regulator of skeletal muscle growth and is conserved in many species, from rodents to humans. Myostatin inactivation can induce skeletal muscle hypertrophy, while its overexpression or systemic administration causes muscle atrophy. As it represents a potential target for stimulating muscle growth and/or preventing muscle wasting, myostatin regulation and functions in the control of muscle mass have been extensively studied. A wealth of data strongly suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression. Moreover, myostatin plays a central role in integrating/mediating anabolic and catabolic responses. Myostatin negatively regulates the activity of the Akt pathway, which promotes protein synthesis, and increases the activity of the ubiquitin–proteasome system to induce atrophy. Several new studies have brought new information on how myostatin may affect both ribosomal biogenesis and translation efficiency of specific mRNA subclasses. In addition, although myostatin has been identified as a modulator of the major catabolic pathways, including the ubiquitin–proteasome and the autophagy–lysosome systems, the underlying mechanisms are only partially understood. The goal of this review is to highlight outstanding questions about myostatin-mediated regulation of the anabolic and catabolic signaling pathways in skeletal muscle. Particular emphasis has been placed on (1) the cross-regulation between myostatin, the growth-promoting pathways and the proteolytic systems; (2) how myostatin inhibition leads to muscle hypertrophy; and (3) the regulation of translation by myostatin.

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Acknowledgments

This study was supported by funds from the Institut National de la Recherche Agronomique (INRA), from the Agence Nationale de la Recherche (ANR Myotrophy).

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Authors and Affiliations

  1. INRA, UMR866 Dynamique Musculaire Et Métabolisme, Université Montpellier 1, Université Montpellier 2, 2 Place Viala, 34060, Montpellier, France

    J. Rodriguez, B. Vernus & A. Bonnieu

  2. INRA, VetAgro Sup, UMR1213 Herbivores, 63122, Saint-Genès-Champanelle, France

    I. Chelh, I. Cassar-Malek & B. Picard

  3. INRA-USC2009, Université Bordeaux 1, Avenue des Facultés, 33405, Talence, France

    A. Hadj Sassi

  4. INRA, UR1037, Fish Physiology and Genomics, Campus de Beaulieu, 35000, Rennes, France

    J. C. Gabillard

  5. INRA, UR1067 Nutrition, Métabolisme, Aquaculture, 64310, Saint-Pée-sur-Nivelle, France

    I. Seiliez

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  1. J. Rodriguez
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  2. B. Vernus
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  7. I. Seiliez
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  9. A. Bonnieu
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Correspondence to A. Bonnieu.

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Rodriguez, J., Vernus, B., Chelh, I. et al. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell. Mol. Life Sci. 71, 4361–4371 (2014). https://doi.org/10.1007/s00018-014-1689-x

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  • DOI: https://doi.org/10.1007/s00018-014-1689-x

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