We previously reported that cellular heparan sulfate proteoglycans (PGs) mediate substantial low-density lipoprotein receptor-independent catabolism of lipoproteins in the presence of lipoprotein lipase (LpL). Relying entirely on experiments with live cells, we now found that the three major classes of cell-surface heparan sulfate PGs exhibit distinct metabolic roles in this pathway. The pathway was not inhibited by digestion of the cell surface with phosphatidylinositol (PI)-specific phospholipase C, indicating that PI-anchored PGs had no detectable involvement. Based on lipoprotein catabolism by a cell line that expresses perlecan but no other PGs, we found that perlecan participated in cell-surface trapping and rapid internalization of LpL-enriched lipoproteins, but exhibited a remarkably slow degradative pathway that is compatible with known properties of perlecan. Using overexpression of syndecan family members in transfected cells, we found that the syndecan family of PGs mediated binding of LpL-enriched lipoproteins, which led to internalization and rapid degradation. We propose that perlecan and syndecan PGs are novel, and metabolically distinct, lipoprotein receptors that could contribute to the clearance in vivo of LpL-enriched particles, such as chylomicron remnants.
|State||Published - 1996|