title: Myostatin inactivation increases myotube size through regulation of translational initiation machinery.
abstract: Myostatin deficiency leads in skeletal muscle overgrowth but the precise molecular mechanisms underlying this hypertrophy are not well understood. In this study, to gain insight into the role of endogenous myostatin in the translational regulation, we used an in vitro model of cultured satellite cells derived from myostatin knock-out mice. Our results show that myostatin knock-out myotubes are larger than control myotubes and that this phenotype is associated with an increased activation of the Akt/mTOR signaling pathway, a known regulator of muscle hypertrophy. These results demonstrate that hypertrophy due to myostatin deficiency is preserved in vitro and suggest that myostatin deletion results in an increased protein synthesis. Accordingly, the rates of global RNA content, polysome formation and protein synthesis are all increased in myostatin-deficient myotubes while they are counteracted by the addition of recombinant myostatin. We furthermore demonstrated that genetic deletion of myostatin stimulates cap-dependent translation by positively regulating assembly of the translation preinitiation complex. Together the data indicate that myostatin controls muscle hypertrophy in part by regulating protein synthesis initiation rates, that is, translational efficiency.
authors.affiliation: INRA, UMR866 Dynamique Musculaire et Métabolisme, Université Montpellier 1, F 34060 Montpellier, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Barbara
authors.initials: B
authors.lastname: Vernus
authors.forename: Mylène
authors.initials: M
authors.lastname: Toubiana
authors.forename: Elodie
authors.initials: E
authors.lastname: Jublanc
authors.forename: Lionel
authors.initials: L
authors.lastname: Tintignac
authors.forename: Serge
authors.initials: S
authors.lastname: Leibovitch
authors.forename: Anne
authors.initials: A
authors.lastname: Bonnieu
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000378:metabolism*; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000235:genetics; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D055435:Myostatin; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases