MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM: Extracellular matrix regulation of skeletal muscle formation1,2

Abstract

Skeletal muscle development and growth is a complex process that involves the interaction of muscle cells with their extracellular environment. Because muscle development involves the interaction of the cell surface and extracellular matrix molecules, research focus has been placed on the proteoglycans. Proteoglycans are macromolecules containing a central core protein with attached carbohydrates, called glycosaminoglycans, that are located at both the cell surface and the extracellular matrix. Research focus has been placed on understanding the mechanisms of the membrane-associated heparan sulfate proteoglycans, syndecan-4 and glypican-1, which are both capable of regulating cellular responsiveness to fibroblast growth factor 2 (FGF2). Fibroblast growth factor 2 is a potent stimulator of muscle cell proliferation and a strong inhibitor of differentiation. Studies on syndecan-4 and glypican-1 show that these proteoglycans differentially regulate muscle cell proliferation, differentiation, and cellular responsiveness to FGF2 with syndecan-4 predominantly modulating muscle cell proliferation and glypican-1 modulating differentiation. Site-directed mutagenesis approaches were used to define the effect of the syndecan-4 and glypican-1 covalently attached side chains on their activity. In general, a functional association was found between the glycosaminoglycan and N-glycosylated chains attached to the central core proteins of syndecan-4 and glypican-1 affecting their regulation of muscle cell proliferation, differentiation, and FGF2 responsiveness. Current research efforts are directed at identifying the cellular signaling pathways modulated by syndecan-4 and glypican-1.