α-syntrophin modulates myogenin expression in differentiating myoblastsα-syntrophin调节myogenin分化成肌细胞中表达.pdf

a-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts 1 1 1 2 2 Min Jeong Kim , Sung Ho Hwang , Jeong A. Lim , Stanley C. Froehner , Marvin E. Adams *, Hye Sun Kim1* 1 Department of Biological Science, Ajou University, Suwon, Korea, 2 Department of Physiology Biophysics, University of Washington, Seattle, Washington, United States of America Abstract Background: a-Syntrophin is a scaffolding protein linking signaling proteins to the sarcolemmal dystrophin complex in mature muscle. However, a-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 a-syntrophin and myogenin, a key muscle regulatory factor. Methods and Findings: The absence of a-syntrophin leads to reduced and delayed myogenin expression. This conclusion is based on experiments using muscle cells isolated from a-syntrophin null mice, muscle regeneration studies in a-syntrophin null mice, experiments in Sol8 cells (a cell line that expresses only low levels of a-syntrophin) and siRNA studies in differentiating C2 cells. In primary cultured myocytes isolated from a-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 a-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 a-syntrophin and in Sol8 cells transfected with a vector to over-express