The chemokine SDF1 controls multiple steps of myogenesis through atypical PKCζ
TLDR
It is 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.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 PKCζ, whereas even after prolonged SDF1 treatment for up to 120 minutes, levels of activated Akt, p38 and PKCα 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 PKCζ peptide pseudosubstrate and/or upon cellular depletion of PKCζ by RNA interference. In conclusion, our findings unravel a previously unknown role of CXCR4-PKCζ signaling in myogenesis. The potent inhibitory effects of SDF1 on myogenic differentiation point to a major function of CXCR4-PKCζ signaling in the control of secondary muscle growth.read more
Citations
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The presumed atypical chemokine receptor CXCR7 signals through Gi/o proteins in primary rodent astrocytes and human glioma cells
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References
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Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle
David Yaffe,Ora Saxel +1 more
TL;DR: The present report describes the isolation of a cloned population of myogenic cells, derived from adult dystrophic mouse muscle, that can proliferate and differentiate in cell culture.
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Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice
Qing Ma,Dan Jones,Paul R. Borghesani,Rosalind A. Segal,Takashi Nagasawa,Tadamitsu Kishimoto,Roderick T. Bronson,Timothy A. Springer +7 more
TL;DR: It is found that mice deficient for CXCR4 die perinatally and display profound defects in the hematopoietic and nervous systems, and Identical defects are observed in mice lacking SDF-1, suggesting a monogamous relationship between CX CR4 and S DF-1.
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