Scavenger Receptor BI Transfers Major Lipoprotein-associated Phospholipids into the Cells

Abstract

The phospholipids of lipoproteins can be transferred to cells by an endocytosis-independent uptake pathway. We analyzed the role of scavenger receptor BI (SR-BI) for the selective cellular phospholipid import. Human monocytes rapidly acquired the pyrene (py)-labeled phospholipids sphingomyelin (SM), phosphatidylcholine, and phosphatidylethanolamine from different donors (low and high density lipoproteins (LDL, HDL), lipid vesicles). The anti-SR-BI antibody directed against the extracellular loop of the membrane protein lowered the cellular import of the phospholipids by 40 -80%. The phospholipid transfer from the lipid vesicles into the monocytes was suppressed by LDL, HDL, and apoprotein AI. Transfection of BHK cells with the cDNA for human SR-BI enhanced the cellular import of the vesicle-derived py-phospholipids by 5-6-fold. In the case of the LDL donors, transfer of py-SM to the transfected cells was stimulated to a greater extent than the uptake of the other py-phospholipids. Similar differences were not observed when the vesicles and HDL were used as phospholipid donors. The concentration of LDL required for the half-maximal phospholipid import was close to the previously reported apparent dissociation constant for LDL binding to SR-BI. The low activation energy of the SR-BI-mediated py-phospholipid import indicated that the transfer occurs entirely in a hydrophobic environment. Disruption of cell membrane caveolae by cyclodextrin treatment reduced the SR-BIcatalyzed incorporation of py-SM, suggesting that intact caveolae are necessary for the phospholipid uptake. In conclusion, SR-BI mediates the selective import of the major lipoprotein-associated phospholipids into the cells, the transfer efficiency being dependent on the structure of the donor lipoprotein.Phospholipids are known to play essential roles in a multitude of cellular processes such as, for example, in intracellular signal transduction (1) and as cofactors of enzyme complexes mediating the proteolytic activation of coagulation proteins (2). Phospholipids are asymmetrically distributed over the two halves of cellular membranes, the asymmetry being generated by proteins catalyzing the transbilayer movement of the lipid molecules (3). Furthermore, there is also lateral separation of the phospholipids within the single monolayers. Indeed, the plasma membranes of many cells contain clusters of sphingolipids, cholesterol, and specific proteins known as caveolae and lipid rafts (4, 5). In order to maintain the physiologic intrabilayer and intramonolayer composition of the phospholipids, the influx and efflux of the phospholipids from the plasma membranes must be tightly regulated.The cellular uptake of phospholipids from extracellular donors is part of this regulatory system. In humans, plasma lipoproteins are a major extracellular source for phospholipids. By means of the endocytosis of low density lipoproteins (LDL), 1 cells also incorporate phospholipids. The capacity of different blood components to take up LDL particles by receptor-mediated en...

Apolipoprotein A-II Modulates the Binding and Selective Lipid Uptake of Reconstituted High Density Lipoprotein by Scavenger Receptor BI

“…It is possible that the values obtained in this experiment (Fig. 2) may in part represent cellular uptake of the phospholipid label, in addition to cell-surface binding, since SR-BI has been reported to exhibit phospholipid uptake activity (42). The three POPCcontaining rHDLs were also studied using particles labeled by 125 I iodination.…”

Phosphatidylcholine Transfer Protein Promotes Apolipoprotein A-I-mediated Lipid Efflux in Chinese Hamster Ovary Cells

“…In contrast to our findings in CHO cells, these investigators found no effect of SR-BI overexpression on apoA-Imediated phospholipid efflux in RAW cells (51) and postulated that this was due to a lack of SR-BI-mediated reuptake of these molecules. Although we have not investigated lipid uptake under these conditions, SR-BI has been shown to mediate efficient uptake of phospholipids in other cell types (52,53). Alternatively, SR-BI may inhibit ABCA1 activity in CHO cells by another mechanism, such as reorganization of the plasma membrane (42).…”

Scavenger Receptor Class B, Type I-mediated Uptake of Various Lipids into Cells

“…It has been shown that selective lipid uptake from HDL occurs during HDL retroendocytosis (18); it is likely that the movement of CE molecules from HDL to the plasma membrane occurs both at the cell surface and in endocytic vesicles. In addition to facilitation of CE uptake, SR-BI mediates uptake of PL from reconstituted HDL particles (16,19). SR-BI can bind a variety of ligands (20,21) and exchangeable apolipoproteins are among them.…”