Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI

Annu Rev Biochem. 1999;68:523-58. doi: 10.1146/annurev.biochem.68.1.523.

Abstract

Risk for cardiovascular disease due to atherosclerosis increases with increasing concentrations of low-density lipoprotein (LDL) cholesterol and is inversely proportional to the levels of high-density lipoprotein (HDL) cholesterol. The receptor-mediated control of plasma LDL levels has been well understood for over two decades and has been a focus for the pharmacologic treatment of hypercholesterolemia. In contrast, the first identification and characterization of a receptor that mediates cellular metabolism of HDL was only recently reported. This receptor, called scavenger receptor class B type I (SR-BI), is a fatty acylated glycoprotein that can cluster in caveolae-like domains on the surfaces of cultured cells. SR-BI mediates selective lipid uptake from HDL to cells. The mechanism of selective lipid uptake is fundamentally different from that of classic receptor-mediated endocytic uptake via coated pits and vesicles (e.g. the LDL receptor pathway) in that it involves efficient receptor-mediated transfer of the lipids, but not the outer shell proteins, from HDL to cells. In mice, SR-BI plays a key role in determining the levels of plasma HDL cholesterol and in mediating the regulated, selective delivery of HDL-cholesterol to steroidogenic tissues and the liver. Significant alterations in SR-BI expression can result in cardiovascular and reproductive disorders. SR-BI may play a similar role in humans; thus, modulation of its activity may provide the basis of future approaches to the treatment and prevention of atherosclerotic disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • CD36 Antigens / metabolism*
  • Cholesterol / metabolism*
  • Humans
  • Lipoproteins, HDL / metabolism
  • Membrane Proteins*
  • Mice
  • Receptors, Immunologic*
  • Receptors, LDL / metabolism
  • Receptors, Lipoprotein*
  • Receptors, Scavenger
  • Scavenger Receptors, Class B

Substances

  • CD36 Antigens
  • Lipoproteins, HDL
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, LDL
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • SCARB1 protein, human
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Cholesterol