Scavenger receptor class B, type I-mediated uptake of various lipids into cells - Influence of the nature of the donor particle interaction with the receptor

Scavenger receptor (SR)-BI is the first molecularly defined receptor for hi gh density lipoprotein (HDL) and it can mediate the selective uptake of cho lesteryl ester into cells. To elucidate the molecular mechanisms by which S R-BI facilitates lipid uptake, we examined the connection between lipid don or particle binding and lipid uptake using kidney COS-7 cells transiently t ransfected with SR-BI. We systematically compared the uptake of [H-3]choles teryl oleoyl ether (CE) and [C-14]sphingomyelin (SM) from apolipoprotein (a po) A-I-containing reconstituted HDL (rHDL) particles and apo-free lipid do nor particles. Although both types of lipid donor could bind to SR-BI, only apo-containing lipid donors exhibited preferential delivery of CE over SM (i.e. nonstoichiometric lipid uptake). In contrast, apo-free lipid donor pa rticles (phospholipid unilamellar vesicles, lipid emulsion particles) gave rise to stoichiometric lipid uptake due to interaction with SR-BI. This app arent whole particle uptake was not due to endocytosis, but rather fusion o f the lipid components of the lipid donor with the cell plasma membrane; th is process is perhaps mediated by a fusogenic motif in the extracellular do main of SR-BI. The interaction of apoA-I with SR-BI not only prevents fusio n of the lipid donor with the plasma membrane but also allows the optimal s elective lipid uptake. A comparison of rHDL particles containing apoA-I and apoE-3 showed that while both particles bound equally well to SR-BI, the a poA-I particle gave similar to2-fold greater CE selective uptake. Catabolis m of all major HDL lipids can occur via SR-BI with the relative selective u ptake rate constants for CE, free cholesterol, triglycerides (triolein), an d phosphatidylcholine being 1, 1.6, 0.7, and 0.2, respectively. It follows that a putative nonpolar channel created by SR-BI between the bound HDL par ticle and the cell plasma membrane is better able to accommodate the uptake of neutral lipids (e.g. cholesterol) relative to polar phospholipids.