Functional specificity of syndecans

Abstract

Syndecans constitute a family of transmembrane heparan sulfate proteoglycans, in which four members have been identified in vertebrates, and Drosophila and C. elegance homologues have been recently cloned. Syndecans have highly conserved amino acid sequences of transmembrane and cytoplasmic domains of the core proteins and a similar exon-intron organization of genomic DNA, suggesting that they share a common ancestral gene. Syndecans mediate the interaction of cells with the microenvironment. Iy is through their heparan sulfate side chains taht these proteoglycans interact with a wide variety of ligands including humoral growth factors such as FGFs, HGF, and midkine, and the constituents of solid extracellular matrix such as fibronectin, tenascin, laminin and collagens . Although these interactions are considered to be involved in regulation of cell proliferation and control of cell behavior in association with the cytoskeletal organization, the cascade for signal transduction through syndecans is still unclear. However, in this regard, recent works have demonstrated dimerization/multimerization of syndecan-3 and -4, phosphorylation of the cytoplasmic domain of syndecan-2, and activation of protein kinase C through its binding to syndecan-4. On the basis of these results, we report here our recent work with murine Lewis lung carcinoma-derived different metastatic clones, showing that cell attachment to fibronectin via both integrin α5β1 and syndecan-2 or only integrin α5β1 results in the distinctly different cytoskeletal organization, i.e., stress fibers or ruffling membrane.