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Mol Cell Biol. 2010 Apr;30(7):1634-49. doi: 10.1128/MCB.01164-09. Epub 2010 Jan 25.

A novel mechanism of sequestering fibroblast growth factor 2 by glypican in lipid rafts, allowing skeletal muscle differentiation.

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  • 1Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.

Abstract

Heparan sulfate proteoglycans (HSPGs) are critical modulators of growth factor activities. Skeletal muscle differentiation is strongly inhibited by fibroblast growth factor 2 (FGF-2). We have shown that HSPGs present at the plasma membrane are expressed in myoblasts and are downregulated during muscle differentiation. An exception is glypican-1, which is present throughout the myogenic process. Myoblasts that do not express glypican-1 exhibit defective differentiation, with an increase in the receptor binding of FGF-2, concomitant with increased signaling. Glypican-1-deficient myoblasts show decreased expression of myogenin, the master gene that controls myogenesis, myosin, and the myoblast fusion index. Reversion of these defects was induced by expression of rat glypican-1. Glypican-1 is the only HSPG localized in lipid raft domains in myoblasts, resulting in the sequestration of FGF-2 away from FGF-2 receptors (FGFRs) located in nonraft domains. A chimeric glypican-1, containing syndecan-1 transmembrane and cytoplasmic domains, is located in nonraft domains interacting with FGFR-IV- and enhanced FGF-2-dependent signaling. Thus, glypican-1 acts as a positive regulator of muscle differentiation by sequestering FGF-2 in lipid rafts and preventing its binding and dependent signaling.

PMID:
20100867
[PubMed - indexed for MEDLINE]
PMCID:
PMC2838066
Free PMC Article

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