Role of scavenger receptors SR-BI and CD36 in selective sterol uptake in the small intestine.
The serum lipoprotein high-density lipoprotein (HDL), which is a ligand of scavenger receptors such as scavenger receptor class B type I (SR-BI) and cluster determinant 36 (CD36), can act as a donor particle for intestinal lipid uptake into the brush border membrane (BBM). Both cholesterol and phospholipids are taken up by the plasma membrane of BBM vesicles (BBMV) and Caco-2 cells in a facilitated (protein-mediated) process. The protein-mediated transfer of cholesterol from reconstituted HDL to BBMV depends on the lipid composition of the HDL. In the presence of sphingomyelin, the transfer of cholesterol is slowed by a factor of about 3 probably due to complex formation between cholesterol and the sphingolipid. It is shown that the mechanism of lipid transfer from reconstituted HDL to either BBMV or Caco-2 cells as the acceptor is consistent with selective lipid uptake: the lipid donor docks at the membrane-resident scavenger receptors which mediate the transfer of lipids between donor and acceptor. Selective lipid uptake implies that lipid, but no apoprotein is transferred from the donor to the BBM, thus excluding endocytotic processes. The two BBM models used here clearly indicate that fusion of donor particles with the BBM can be ruled out as a major mechanism contributing to intestinal lipid uptake. Here we demonstrate that CD36, another member of the family of scavenger receptors, is present in rabbit and human BBM vesicles. This receptor mediates the uptake of free cholesterol, but not of esterified cholesterol, the uptake of which is mediated exclusively by SR-BI. More than one scavenger receptor appears to be involved in the uptake of free cholesterol with SR-BI contributing about 25% and CD36 about 35%. There is another yet unidentified protein accounting for the remaining 30 to 40%.
Werder
M
M
Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Center, Universitätstrasse 16, CH-8092 Zurich, Switzerland.
Han
C H
CH
Wehrli
E
E
Bimmler
D
D
Schulthess
G
G
Hauser
H
H
D000230:Adenocarcinoma; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007421:Intestine, Small / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins; D051379:Mice; D016253:Microscopy, Immunoelectron; D008871:Microvilli / Q000378:metabolism* / Q000648:ultrastructure; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013261:Sterols / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018955:CD36 Antigens; D008076:Cholesterol, HDL; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013261:Sterols; D002784:Cholesterol