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BMP signaling controls muscle mass

Official URL:https://doi.org/10.1038/ng.2772
PubMed:View item in PubMed
Creators Name:Sartori, R. and Schirwis, E. and Blaauw, B. and Bortolanza, S. and Zhao, J. and Enzo, E. and Stantzou, A. and Mouisel, E. and Toniolo, L. and Ferry, A. and Stricker, S. and Goldberg, A.L. and Dupont, S. and Piccolo, S. and Amthor, H. and Sandri, M.
Journal Title:Nature Genetics
Journal Abbreviation:Nat Genet
Page Range:1309-1318
Date:November 2013
Keywords:Bone Morphogenetic Proteins, Cell Line, Enzyme Activation, Gene Expression Profiling, HEK293 Cells, Muscular Atrophy, Myostatin, RNA Interference, Signal Transduction, Skeletal Muscle, Smad1 Protein, Smad4 Protein, Smad5 Protein, Smad8 Protein, Small Interfering RNA, Ubiquitin-Protein Ligases, Animals, Mice
Abstract:Cell size is determined by the balance between protein synthesis and degradation. This equilibrium is affected by hormones, nutrients, energy levels, mechanical stress and cytokines. Mutations that inactivate myostatin lead to excessive muscle growth in animals and humans, but the signals and pathways responsible for this hypertrophy remain largely unknown. Here we show that bone morphogenetic protein (BMP) signaling, acting through Smad1, Smad5 and Smad8 (Smad1/5/8), is the fundamental hypertrophic signal in mice. Inhibition of BMP signaling causes muscle atrophy, abolishes the hypertrophic phenotype of myostatin-deficient mice and strongly exacerbates the effects of denervation and fasting. BMP-Smad1/5/8 signaling negatively regulates a gene (Fbxo30) that encodes a ubiquitin ligase required for muscle loss, which we named muscle ubiquitin ligase of the SCF complex in atrophy-1 (MUSA1). Collectively, these data identify a critical role for the BMP pathway in adult muscle maintenance, growth and atrophy.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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