Scavenger receptor BI transfers major lipoprotein-associated phospholipids into the cells.
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-BI-catalyzed 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.
Urban
S
S
Physiologisches Institut der Universität München, Schillerstrasse 44, 80336 München, Germany.
Zieseniss
S
S
Werder
M
M
Hauser
H
H
Budzinski
R
R
Engelmann
B
B
D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens; D021941:Caveolae / Q000378:metabolism; D021961:Cell Membrane Structures / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013109:Sphingomyelins / Q000378:metabolism; D013696:Temperature
D018955:CD36 Antigens; D008074:Lipoproteins; D008565:Membrane Proteins; D010743:Phospholipids; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013109:Sphingomyelins