The syndecan family of proteoglycans. Novel receptors mediating internalization of atherogenic lipoproteins in vitro.

I V Fuki; K M Kuhn; I R Lomazov; V L Rothman; G P Tuszynski; R V Iozzo; T L Swenson; E A Fisher; K J Williams

doi:10.1172/JCI119685

The syndecan family of proteoglycans. Novel receptors mediating internalization of atherogenic lipoproteins in vitro.

I V Fuki, K M Kuhn, I R Lomazov, V L Rothman, G P Tuszynski, R V Iozzo, T L Swenson, E A Fisher, and K J Williams

Published September 15, 1997 - More info

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Abstract

Cell-surface heparan sulfate proteoglycans have been shown to participate in lipoprotein catabolism, but the roles of specific proteoglycan classes have not been examined previously. Here, we studied the involvement of the syndecan proteoglycan family. First, transfection of CHO cells with expression vectors for several syndecan core proteins produced parallel increases in the cell association and degradation of lipoproteins enriched in lipoprotein lipase, a heparan-binding protein. Second, a chimeric construct, FcR-Synd1, that consists of the ectodomain of the IgG Fc receptor Ia linked to the highly conserved transmembrane and cytoplasmic domains of syndecan-1 directly mediated efficient internalization, in a process triggered by ligand clustering. Third, internalization of lipase-enriched lipoproteins via syndecan-1 and of clustered IgGs via the chimera showed identical kinetics (t1/2 = 1 h) and identical dose-response sensitivities to cytochalasin B, which disrupts microfilaments, and to genistein, which inhibits tyrosine kinases. In contrast, internalization of the receptor-associated protein, which proceeds via coated pits, showed a t1/2 < 15 min, limited sensitivity 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 act as receptors for atherogenic lipoproteins and other ligands in vivo.

The syndecan family of proteoglycans. Novel receptors mediating internalization of atherogenic lipoproteins in vitro.

I V Fuki, K M Kuhn, I R Lomazov, V L Rothman, G P Tuszynski, R V Iozzo, T L Swenson, E A Fisher, and K J Williams

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The syndecan family of proteoglycans. Novel receptors mediating internalization of atherogenic lipoproteins in vitro.

I V Fuki, K M Kuhn, I R Lomazov, V L Rothman, G P Tuszynski, R V Iozzo, T L Swenson, E A Fisher, and K J Williams

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