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PMID:20100867

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Citation

Gutiérrez, J and Brandan, E (2010) A novel mechanism of sequestering fibroblast growth factor 2 by glypican in lipid rafts, allowing skeletal muscle differentiation. Mol. Cell. Biol. 30:1634-49

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.

Links

PubMed PMC2838066 Online version:10.1128/MCB.01164-09

Keywords

Animals; Cell Differentiation/physiology; Cell Line; Extracellular Matrix/metabolism; Fibroblast Growth Factor 2/genetics; Fibroblast Growth Factor 2/metabolism; Glypicans/genetics; Glypicans/metabolism; Laminin/metabolism; Membrane Microdomains/chemistry; Membrane Microdomains/metabolism; Mice; Muscle, Skeletal/cytology; Muscle, Skeletal/physiology; Myoblasts/cytology; Myoblasts/physiology; Myogenin/metabolism; Rats; Receptors, Fibroblast Growth Factor/genetics; Receptors, Fibroblast Growth Factor/metabolism; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GPC1

located_in

GO:0045121: membrane raft

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GPC1

located_in

GO:0031012: extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GPC1

enables

GO:0017134: fibroblast growth factor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GPC1

enables

GO:0043236: laminin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GPC1

involved_in

GO:2001016: positive regulation of skeletal muscle cell differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GPC1

involved_in

GO:0040037: negative regulation of fibroblast growth factor receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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