| First Author | Gutiérrez J | Year | 2010 |
| Journal | Mol Cell Biol | Volume | 30 |
| Issue | 7 | Pages | 1634-49 |
| PubMed ID | 20100867 | Mgi Jnum | J:161728 |
| Mgi Id | MGI:4461098 | Doi | 10.1128/MCB.01164-09 |
| Citation | Gutierrez J, et al. (2010) A novel mechanism of sequestering fibroblast growth factor 2 by glypican in lipid rafts, allowing skeletal muscle differentiation. Mol Cell Biol 30(7):1634-49 |
| abstractText | 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. |
