The chemokine SDF1 controls multiple steps of myogenesis through atypical PKCzeta

Veysel Odemis1, Karina Boosmann, Maja Theresa Dieterlen

  • 1Institute of Anatomy, Medical Faculty, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany.

Journal of Cell Science
|November 1, 2007
PubMed

Insights

The chemokine SDF1 (stromal cell-derived factor 1) and its receptor CXCR4 regulate muscle growth by inhibiting differentiation and promoting proliferation and migration via PKCzeta signaling.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Muscle Development

Background:

  • Mice lacking the SDF1-chemokine-receptor CXCR4 show significant defects in secondary limb myogenesis.
  • SDF1 is a chemokine implicated in various biological processes, but its specific role in muscle development requires further elucidation.

Purpose of the Study:

  • To investigate the effects of SDF1 on the proliferation, migration, and myogenic differentiation of mouse C2C12 myoblasts.
  • To characterize the signaling pathways activated by SDF1-CXCR4 signaling in myogenesis.

Main Methods:

  • Analysis of C2C12 cell proliferation, migration, and differentiation markers (MyoD, myosin heavy chain, myogenin).
  • Assessment of signaling pathway activation (Erk, PKCzeta, Akt, p38, PKCalpha/beta) via phosphorylation.
  • Pharmacological inhibition (UO126, myristoylated PKCzeta peptide) and genetic depletion (RNA interference) of signaling molecules.

Main Results:

  • SDF1 significantly stimulates proliferation and migration of C2C12 cells, comparable to FGF2 and HGF.
  • SDF1 inhibits myogenic differentiation in C2C12 cells and primary myoblasts.
  • SDF1 activates Erk and PKCzeta, but not Akt, p38, or PKCalpha/beta.
  • Erk inhibition blocks SDF1-induced proliferation/migration but not differentiation inhibition.
  • PKCzeta inhibition or depletion abrogates all SDF1 effects on proliferation, migration, and differentiation.

Conclusions:

  • CXCR4-PKCzeta signaling plays a previously unrecognized role in myogenesis.
  • SDF1's potent inhibition of myogenic differentiation highlights CXCR4-PKCzeta signaling's function in controlling secondary muscle growth.

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