THE SYNDECAN FAMILY OF PROTEOGLYCANS - NOVEL RECEPTORS MEDIATING INTERNALIZATION OF ATHEROGENIC LIPOPROTEINS IN-VITRO

Cell-surface heparan sulfate proteoglycans have been shown to particip ate in lipoprotein catabolism, but the roles of specific proteoglycan classes have not been examined previously. Here, we studied the involv ement of the syndecan proteoglycan family. First, transfection of CHO cells with expression vectors for several syndecan core proteins produ ced parallel increases in the cell association and degradation of lipo proteins enriched in lipoprotein lipase, a heparan-binding protein. Se cond, a chimeric construct, FcR-Synd1, that consists of the ectodomain of the IgG Fc receptor Ia linked to the highly conserved transmembran e and cytoplasmic domains of syndecan-1 directly mediated efficient in ternalization, in a process triggered by ligand clustering. Third, int ernalization of lipase-enriched lipoproteins via syndecan-1 and of clu stered IgGs via the chimera showed identical kinetics (t(1/2) = 1 h) a nd identical dose-response sensitivities to cytochalasin B, which disr upts microfilaments, and to genistein, which inhibits tyrosine kinases . In contrast, internalization of the receptor-associated protein, whi ch proceeds via coated pits, showed a t(1/2) < 15 min, Limited sensiti vity to cytochalasin B, and complete insensitivity to genistein. Thus, syndecan proteoglycans can directly mediate ligand catabolism through a pathway with characteristics distinct from coated pits, and might a ct as receptors for atherogenic lipoproteins and other ligands in vivo .