High density lipoprotein receptors, binding proteins, and ligands

Several HDL binding proteins, quite disparate in structure, have recently b een cloned and their role in HDL metabolism is currently being assessed. Hi gh density lipoprotein binding protein, HBP (vigilin), which lacks a transm embrane domain is responsive to cell cholesterol levels, but its physiologi cal significance remains unknown. On the other hand much is known about SR- B1, a member of the class B scavenger receptors. The level of SR-B1 express ion correlates with both the selective transfer of cholesteryl ester into c ells and cholesterol efflux from cells, the transfers probably mediated aft er docking of HDL at the cell surface. SR-B1 exhibits broad Ligand specific ity and, in animal models, appears to be regulated by the action of pituita ry hormones that stimulate steroidogenesis, suggesting an important role fo r steroid hormone production in supplying precursor cholesterol. Another ca ndidate HDL receptor, HBP, one of a pair of liver HDL binding proteins, sho ws high sequence homolog with adhesion molecules, particularly activated le ukocyte-cell adhesion molecule (ALCAM). When HBP is overexpressed in cells, HDL binding increases. After PMA-induced differentiation of monocytes into macrophages, HB2 mRNA is strikingly elevated, which correlates with increa sed binding of HDL, but is down-regulated by cholesterol loading of macroph ages. The ligand specificity of the HDL receptors, confounded by nonspecifi c lipid interactions, remains controversial. Their affinity for apoA-I vers us apoA-I/A-II-rich HDL particles has clinical implications; both specific sequences in apoA-I and amphipathic alpha-helices may determine binding eve nts. Post-receptor-mediated signalling events may regulate cell functions w hich, although not primarily related to lipid transport, nevertheless prote ct against coronary artery disease. Growing evidence for the involvement of lipid-poor apoA-I as a mediator of such pathways is also discussed.