Lipid free apolipoprotein E binds to the class B Type I scavenger receptor I (SR-BI) and enhances cholesteryl ester uptake from lipoproteins

J Biol Chem. 2002 Sep 27;277(39):36092-9. doi: 10.1074/jbc.M201943200. Epub 2002 Jul 22.

Abstract

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.

MeSH terms

  • Apolipoproteins E / metabolism*
  • Binding Sites
  • Binding, Competitive
  • CD36 Antigens / chemistry
  • CD36 Antigens / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cholesterol Esters / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Glycosides / metabolism
  • Humans
  • Hydrolysis
  • Ligands
  • Lipid Metabolism
  • Lipoproteins / metabolism*
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / metabolism
  • Membrane Proteins*
  • Protein Binding
  • Receptors, Immunologic*
  • Receptors, Lipoprotein*
  • Receptors, Scavenger
  • Recombinant Proteins / metabolism
  • Scavenger Receptors, Class B
  • Thrombin / metabolism
  • Tumor Cells, Cultured

Substances

  • Apolipoproteins E
  • CD36 Antigens
  • Cholesterol Esters
  • Glycosides
  • Ligands
  • Lipoproteins
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Recombinant Proteins
  • SCARB1 protein, human
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • very high density lipoproteins
  • xylosides
  • Thrombin