Review

High density lipoprotein receptors, binding proteins, and ligands

Several HDL binding proteins, quite disparate in structure, have recently been cloned and their role in HDL metabolism is currently being assessed. High density lipoprotein binding protein, HBP (vigilin), which lacks a transmembrane domain is responsive to cell cholesterol levels, but its physiological 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 expression correlates with both the selective transfer of cholesteryl ester into cells and cholesterol efflux from cells, the transfers probably mediated after docking of HDL at the cell surface. SR-B1 exhibits broad ligand specificity and, in animal models, appears to be regulated by the action of pituitary hormones that stimulate steroidogenesis, suggesting an important role for steroid hormone production in supplying precursor cholesterol. Another candidate HDL receptor, HB₂, one of a pair of liver HDL binding proteins, shows high sequence homology with adhesion molecules, particularly activated leukocyte-cell adhesion molecule (ALCAM). When HB₂ is overexpressed in cells, HDL binding increases. After PMA-induced differentiation of monocytes into macrophages, HB₂ mRNA is strikingly elevated, which correlates with increased binding of HDL, but is down-regulated by cholesterol loading of macrophages. The ligand specificity of the HDL receptors, confounded by nonspecific lipid interactions, remains controversial. Their affinity for apoA-I versus apoA-I/A-II-rich HDL particles has clinical implications; both specific sequences in apoA-I and amphipathic -helices may determine binding events. Post-receptor-mediated signalling events may regulate cell functions which, although not primarily related to lipid transport, nevertheless protect against coronary artery disease. Growing evidence for the involvement of lipid-poor apoA-I as a mediator of such pathways is also discussed.—Fidge, N. H. High density lipoprotein receptors, binding proteins, and ligands. J. Lipid Res. 1999. 40: 187–201.

Supplementary key words: HBP, SR-BI, HB₂, ligands, biochemical signalling, activated leukocyte-cell adhesion molecule, cholesterol, apolipoprotein E

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