title: Α-syntrophin modulates myogenin expression in differentiating myoblasts.
abstract: BACKGROUND
  α-Syntrophin is a scaffolding protein linking signaling proteins to the sarcolemmal dystrophin complex in mature muscle. However, α-syntrophin is also expressed in differentiating myoblasts during the early stages of muscle differentiation. In this study, we examined the relationship between the expression of α-syntrophin and myogenin, a key muscle regulatory factor.
  
  
  RESULTS
  The absence of α-syntrophin leads to reduced and delayed myogenin expression. This conclusion is based on experiments using muscle cells isolated from α-syntrophin null mice, muscle regeneration studies in α-syntrophin null mice, experiments in Sol8 cells (a cell line that expresses only low levels of α-syntrophin) and siRNA studies in differentiating C2 cells. In primary cultured myocytes isolated from α-syntrophin null mice, the level of myogenin was less than 50% that from wild type myocytes (p<0.005) 40 h after differentiation induction. In regenerating muscle, the expression of myogenin in the α-syntrophin null muscle was reduced to approximately 25% that of wild type muscle (p<0.005). Conversely, myogenin expression is enhanced in primary cultures of myoblasts isolated from a transgenic mouse over-expressing α-syntrophin and in Sol8 cells transfected with a vector to over-express α-syntrophin. Moreover, we find that myogenin mRNA is reduced in the absence of α-syntrophin and increased by α-syntrophin over-expression. Immunofluorescence microscopy shows that α-syntrophin is localized to the nuclei of differentiating myoblasts. Finally, immunoprecipitation experiments demonstrate that α-syntrophin associates with Mixed-Lineage Leukemia 5, a regulator of myogenin expression.
  
  
  CONCLUSIONS
  We conclude that α-syntrophin plays an important role in regulating myogenesis by modulating myogenin expression.
authors.affiliation: Department of Biological Science, Ajou University, Suwon, Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Hwang
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Lim
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Froehner
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Adams
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002454:Cell Differentiation; D005260:Female; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D032342:Muscle Cells / Q000166:cytology; D009124:Muscle Proteins / Q000235:genetics*; D009132:Muscles / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology*; D018008:Myogenin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D018008:Myogenin; D020033:Protein Isoforms; D034741:RNA, Small Interfering; C091825:syntrophin alpha1