title: Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation.
abstract: BACKGROUND
  Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of Rho signaling (STARS) is an actin binding protein that regulates the transcription of genes involved in muscle cell growth, structure and function via the stimulation of actin polymerization and activation of serum-response factor (SRF) signaling. STARS mediates cell proliferation in smooth and cardiac muscle models; however, whether STARS overexpression enhances cell proliferation and differentiation has not been investigated in skeletal muscle cells.
  
  
  RESULTS
  We demonstrate for the first time that STARS overexpression enhances differentiation but not proliferation in C2C12 mouse skeletal muscle cells. Increased differentiation was associated with an increase in the gene levels of the myogenic differentiation markers Ckm, Ckmt2 and Myh4, the differentiation factor Igf2 and the myogenic regulatory factors (MRFs) Myf5 and Myf6. Exposing C2C12 cells to CCG-1423, a pharmacological inhibitor of SRF preventing the nuclear translocation of its co-factor MRTF-A, had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism.
  
  
  CONCLUSIONS
  These findings position STARS as an important regulator of skeletal muscle growth and regeneration.
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University Burwood, VIC, Australia.
authors.forename: Marita A
authors.initials: MA
authors.lastname: Wallace
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University Burwood, VIC, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Della Gatta
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University Burwood, VIC, Australia.
authors.forename: Bilal
authors.initials: B
authors.lastname: Ahmad Mir
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University Burwood, VIC, Australia.
authors.forename: Greg M
authors.initials: GM
authors.lastname: Kowalski
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne Parkville, VIC, Australia.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kloehn
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne Parkville, VIC, Australia.
authors.forename: Malcom J
authors.initials: MJ
authors.lastname: McConville
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University Burwood, VIC, Australia.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University Burwood, VIC, Australia.
authors.forename: Séverine
authors.initials: S
authors.lastname: Lamon
keywords: differentiation; myogenesis; proliferation; regeneration; skeletal muscle