CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS - DYNAMIC MOLECULES MEDIATING LIGAND CATABOLISM

Though sometimes regarded as merely passive, space-filling components, proteoglycans are in fact metabolically active molecules with carbohy drate and protein domains that are highly conserved throughout evoluti on, indicating specific, crucial functions. Here we review recent evid ence that heparan sulfate proteoglycans, particularly syndecans and pe rlecan, are able to mediate directly the internalization of lipoprotei ns and other ligands, without requiring the participation of LDL recep tor family members. Thus, heparan sulfate proteoglycans can function a s receptors. in the case of syndecan heparan sulfate proteoglycans, ef ficient internalization is triggered by clustering of the transmembran e and cytoplasmic domains and then proceeds through a noncoated pit pa thway, possibly caveolae. The physiologic and pathophysiologic importa nce of these direct heparan sulfate proteoglycan-mediated catabolic pa thways in the liver and in the arterial wall in vivo remains to be set tled.