Lipid free apolipoprotein E binds to the class B Type I scavenger receptor I (SR-BI) and enhances cholesteryl ester uptake from lipoproteins.
The Class B type I scavenger receptor I (SR-BI) is a physiologically relevant high density lipoprotein (HDL) receptor that can mediate selective cholesteryl ester (CE) uptake by cells. Direct interaction of apolipoprotein E (apoE) with this receptor has never been demonstrated, and its implication in CE uptake is still controversial. By using a human adrenal cell line (NCI-H295R), we have addressed the role of apoE in binding to SR-BI and in selective CE uptake from lipoproteins to cells. This cell line does not secrete apoE and SR-BI is its major HDL-binding protein. We can now provide evidence that 1) free apoE is a ligand for SR-BI, 2) apoE associated to lipids or in lipoproteins does not modulate binding or CE-selective uptake by the SR-BI pathway, and 3) the direct interaction of free apoE to SR-BI leads to an increase in CE uptake from lipoproteins of both low and high densities. We propose that this direct interaction could modify SR-BI structure in cell membranes and potentiate CE uptake.
Unité INSERM U 545, Institut Pasteur de Lille, Faculté de Pharmacie, Université Lille 2, 1 rue du Professeur Calmette, 59019 Lille cedex, France.
Stéphanie
S
Bultel-Brienne
Sophie
S
Lestavel
Antoine
A
Pilon
Isabelle
I
Laffont
Anne
A
Tailleux
Jean-Charles
JC
Fruchart
Gérard
G
Siest
Véronique
V
Clavey
D001057:Apolipoproteins E / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D018955:CD36 Antigens / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002788:Cholesterol Esters / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006027:Glycosides / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008024:Ligands; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008565:Membrane Proteins; D011485:Protein Binding; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D051122:Scavenger Receptors, Class B; D013917:Thrombin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001057:Apolipoproteins E; D018955:CD36 Antigens; D002788:Cholesterol Esters; D006027:Glycosides; D008024:Ligands; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C026277:very high density lipoproteins; C010807:xylosides; D013917:Thrombin