Affordable Access

deepdyve-link
Publisher Website

BMP signaling controls muscle mass.

Authors
  • Sartori, Roberta1
  • Schirwis, Elija
  • Blaauw, Bert
  • Bortolanza, Sergia
  • Zhao, Jinghui
  • Enzo, Elena
  • Stantzou, Amalia
  • Mouisel, Etienne
  • Toniolo, Luana
  • Ferry, Arnaud
  • Stricker, Sigmar
  • Goldberg, Alfred L
  • Dupont, Sirio
  • Piccolo, Stefano
  • Amthor, Helge
  • Sandri, Marco
  • 1 1] Dulbecco Telethon Institute at the Venetian Institute of Molecular Medicine, Padova, Italy. [2] Department of Biomedical Sciences, University of Padova, Padova, Italy. [3]. , (Italy)
Type
Published Article
Journal
Nature Genetics
Publisher
Springer Nature
Publication Date
Nov 01, 2013
Volume
45
Issue
11
Pages
1309–1318
Identifiers
DOI: 10.1038/ng.2772
PMID: 24076600
Source
Medline
Language
English
License
Unknown

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.

Report this publication

Statistics

Seen <100 times