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    Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation

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    Author
    Wallace, MA; Della Gatta, PA; Mir, BA; Kowalski, GM; Kloehn, J; McConville, MJ; Russell, AP; Lamon, S
    Date
    2016-02-08
    Source Title
    Frontiers in Physiology
    Publisher
    FRONTIERS MEDIA SA
    University of Melbourne Author/s
    McConville, Malcolm; KLOEHN, JOACHIM
    Affiliation
    Biochemistry and Molecular Biology
    Metadata
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    Document Type
    Journal Article
    Citations
    Wallace, M. A., Della Gatta, P. A., Mir, B. A., Kowalski, G. M., Kloehn, J., McConville, M. J., Russell, A. P. & Lamon, S. (2016). Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation. FRONTIERS IN PHYSIOLOGY, 7 (FEB), https://doi.org/10.3389/fphys.2016.00007.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258269
    DOI
    10.3389/fphys.2016.00007
    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. CONCLUSION: These findings position STARS as an important regulator of skeletal muscle growth and regeneration.

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