APOLIPOPROTEINS OF HDL CAN DIRECTLY MEDIATE BINDING TO THE SCAVENGER RECEPTOR SR-BI, AN HDL RECEPTOR THAT MEDIATES SELECTIVE LIPID UPTAKE

The class B type I scavenger receptor, SR-BI, binds HDL, mediates sele ctive uptake of HDL cholesteryl esters by cultured cells, and its expr ession is coordinately regulated with steroidogenesis in several endoc rine tissues (adrenal, ovary, testes). SR-BI can also bind LDL and ani onic phospholipids, which raised the possibility that HDL apolipoprote ins might not participate directly in HDL binding. We have examined th e ability of individual human HDL apolipoproteins (apoA-I, apoA-II, an d apoC-III) reconstituted into phospholipid/unesterified cholesterol c omplexes to bind to murine SR-BI (mSR-BI) expressed in stably transfec ted cultured cells. All three apolipoprotein/phospholipid/unesterified cholesterol complexes specifically associated with mSR-BI expressing cells with high affinity and competed for the binding of HDL, while ap olipoprotein-free complexes did not. Furthermore, lipid-free forms of these soluble apolipoproteins also competed for HDL and apolipoprotein /phospholipid/cholesterol complex association with mSR-BI, but locust high density lipophorin and bovine serum albumin were not effective co mpetitors. Thus, all three of the HDL apolipoproteins (apoA-I, apoA-II , and apoC-III) tested can directly mediate binding to mSR-BI, and thi s multiligand apolipoprotein receptor may be responsible for at least some of the multilipoprotein and apolipoprotein binding activity previ ously observed in cells and tissues.