The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein.
The low-density-lipoprotein (LDL) receptor is a cell-surface protein that plays an important part in the metabolism of cholesterol by mediating the uptake of LDL from plasma into cells. Although LDL particles bind to the LDL receptor through their apolipoprotein B (apo B) and apolipoprotein E (apo E) moieties, other apo E-containing particles, like chylomicron remnants, are not dependent on the LDL receptor for uptake into cells. Chylomicrons formed in the intestinal mucosa during the absorption of the products of digestion, are processed by the peripheral circulation by lipoprotein lipase, which catalyses the breakdown of triglycerides in chylomicrons to free fatty acids and glycerol. The resulting chylomicron remnants, which are cholesterol-rich lipoproteins, are subsequently taken up in the liver. A second distinct protein that binds to apo E-containing lipoproteins, but not to LDL, has been proposed to be the receptor mediating the clearance of chylomicron remnants from the plasma. This protein has a relative molecular mass (Mr) of 56,000 (56K). More recent studies have failed, however, to establish whether this protein is a cell-surface receptor. Here we describe crosslinking experiments in which apo E liposomes were found to bind specifically to the cell surface of hepG2 cells and to human liver membranes. The size and immunological cross-reactivity of the protein to which the liposomes bound was indistinguishable from that of the recently cloned and sequenced LDL-receptor-related protein, LRP. We therefore conclude that the LRP might function as an apo E receptor.
Medical Clinic, University Hospital Eppendorf, Hamburg.
U
U
Beisiegel
W
W
Weber
G
G
Ihrke
J
J
Herz
K K
KK
Stanley
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D011971:Receptors, Immunologic / Q000302:isolation & purification / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis
D001057:Apolipoproteins E; D008081:Liposomes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D014280:Triglycerides