The expressed human hepatic receptor for low-density lipoproteins differs from the fibroblast low-density lipoprotein receptor.
The role of the cellular receptor for the low-density lipoproteins (LDL) in cholesterol transport was initially defined through the study of nonhepatic cells in vitro. Since the liver is central in plasma lipoprotein metabolism, an investigation of hepatic lipoprotein receptors is important for understanding normal lipoprotein transport. Utilizing human hepatic and fibroblast membranes, the characteristics of receptors for LDL from hepatic and nonhepatic tissues were directly compared. Human hepatic membranes reversibly bound LDL within 5 min. Although both fibroblast and hepatic membranes saturably bound LDL at 37 degrees C, the fibroblast LDL receptor affinity (Kd = 2.5 X 10(-8) M) and number (5.5 X 10(12) sites/mg membrane protein) were greater than the hepatic receptor affinity (Kd = 10.8 X 10(-8) M) and number (0.5 X 10(12) sites/mg membrane protein). In contrast to the fibroblast LDL receptor which was unable to bind LDL in the presence of EDTA, the hepatic LDL receptor binding of LDL was only partially blocked by EDTA. The binding of LDL to its hepatic receptor is highly temperature-dependent, and studies utilizing both radiolabeled LDL and colloidal gold-labeled LDL indicate that little, if any, binding of LDL hepatic membranes occur at 0-4 degrees C. The hepatic membrane receptor(s) (Mr approximately equal to 270 000 and 330 000) differ from that of the fibroblast LDL receptor (Mr approximately equal to 130 000) and these proteins are present in hepatic membranes from a patient lacking the fibroblast LDL receptor. These data indicate that an expressed hepatic LDL receptor has unique properties different from those of the fibroblast LDL receptor and that the expressed protein(s) is genetically distinct from the fibroblast receptor.
Hoeg
J M
JM
Demosky
S J
SJ
Lackner
K J
KJ
Osborne
J C
JC
Oliver
C
C
Brewer
H B
HB
D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D005347:Fibroblasts / Q000032:analysis*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000032:analysis*; D008433:Mathematics; D008854:Microscopy, Electron; D008970:Molecular Weight; D011973:Receptors, LDL / Q000032:analysis*
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D004492:Edetic Acid; D002118:Calcium