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J. Cell Sci. 120 (22): 4050-4059

Research Article

The chemokine SDF1 controls multiple steps of myogenesis through atypical PKC{zeta}

Veysel Ödemis1,*, Karina Boosmann1,*, Maja Theresa Dieterlen2, and Jürgen Engele1,{ddagger}

1 Institute of Anatomy, Medical Faculty, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany
2 Department of Neurology, University of Leipzig, Liebigstr. 22a, 04103 Leipzig, Germany

{ddagger} Author for correspondence (e-mail: engj{at}medizin.uni-leipzig.de)

Accepted for publication 14 September 2007.

Abstract: Mice deficient in the SDF1-chemokine-receptor CXCR4, exhibit severe defects of secondary limb myogenesis. To further elucidate the role of SDF1 in muscle development, we have now analyzed putative effects of this chemokine on proliferation, migration and myogenic differentiation of mouse C2C12 myogenic progenitor/myoblast cells. In addition, we have characterized the signaling pathways employed by SDF1-CXCR4 to control myogenesis. We found that SDF1 stimulates proliferation and induces migration of C2C12 cells with a potency similar to that of FGF2 and HGF, which both represent prototypical extracellular regulators of myogenesis. In addition, SDF1 inhibits myogenic differentiation in both C2C12 cells and primary myoblasts, as assessed by MyoD, myosin heavy chain and/or myogenin expression. Regarding signaling pathways, C2C12 cells responded to SDF1 with activation (phosphorylation) of Erk and PKC{zeta}, whereas even after prolonged SDF1 treatment for up to 120 minutes, levels of activated Akt, p38 and PKC{alpha} or PKCβ remained unaffected. Preventing activation of the classic MAP kinase cascade with the Erk inhibitor UO126 abolished SDF1-induced proliferation and migration of C2C12 cells but not the inhibitory action of SDF1 on myogenic differentiation. Moreover, the effects of SDF1 on proliferation, migration and differentiation of C2C12 cells were all abrogated in the presence of myristoylated PKC{zeta} peptide pseudosubstrate and/or upon cellular depletion of PKC{zeta} by RNA interference. In conclusion, our findings unravel a previously unknown role of CXCR4-PKC{zeta} signaling in myogenesis. The potent inhibitory effects of SDF1 on myogenic differentiation point to a major function of CXCR4-PKC{zeta} signaling in the control of secondary muscle growth.

Key Words: CXCR4 • Myogenin • MyoD • Myosin heavy chain • Myoblasts

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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