The role of syndecan-4 and attached glycosaminoglycan chains on myogenic satellite cell growth

Abstract

The syndecans are a family of cell-surface heparan sulfate proteoglycans consisting of a core protein with covalently attached glycosaminoglycan (GAG) chains. Syndecan-4 expression in skeletal muscle is increased in growth-selected animals during proliferation. Previous studies have suggested that cell-surface heparan sulfate proteoglycans like syndecan-4 are involved in fibroblast growth factor 2 (FGF2) signaling by FGF2 binding to the heparan sulfate chains. Fibroblast growth factor 2 is a potent stimulator of muscle proliferation and an intense inhibitor of differentiation. To investigate the functional contribution of the attached syndecan-4 GAG chains, a turkey syndecan-4 full length cDNA was cloned and mutated at two or all three potential GAG attachment sites at Ser 38, Ser 65, and Ser 67 resulting in all possible one-chain mutants and a no-chain mutant. Turkey satellite cells were transfected with the wild-type syndecan-4, one-chain mutants, no-chain mutant, or the empty vector and assayed for cell proliferation, differentiation, and FGF2 responsiveness. The wild-type syndecan-4, one-chain mutants, and no-chain mutant inhibited cell proliferation and delayed initial differentiation but did not alter FGF2 responsiveness or function through the mitogen-activated protein kinase pathway. There was no difference between the wild-type syndecan-4, one-chain, and no-chain mutants during these stages. These data suggest that syndecan-4 functions in an FGF2-independent manner and the GAG chains attached to the syndecan-4 core protein are not required for syndecan-4 to affect turkey satellite cell proliferation and the initial differentiation.