BMP signaling controls muscle mass

Item Type:	Article
Title:	BMP signaling controls muscle mass
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.
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.
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
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	45
Number:	11
Page Range:	1309-1318
Date:	November 2013
Official Publication:	https://doi.org/10.1038/ng.2772
PubMed:	View item in PubMed

Repository Staff Only: item control page