SR-BII, an isoform of the scavenger receptor BI containing an alternate cytoplasmic tail, mediates lipid transfer between high density lipoprotein and cells

J Biol Chem. 1998 Jun 12;273(24):15241-8. doi: 10.1074/jbc.273.24.15241.

Abstract

The scavenger receptor class B, type I (SR-BI), binds high density lipoprotein (HDL) and mediates selective uptake of cholesteryl ester from HDL and HDL-dependent cholesterol efflux from cells. We recently identified a new mRNA variant that differs from the previously characterized form in that the encoded C-terminal cytoplasmic domain is almost completely different. In the present study, we demonstrate that the mRNAs for mouse SR-BI and SR-BII (previously termed SR-BI.2) are the alternatively spliced products of a single gene. The translation products predicted from human, bovine, mouse, hamster, and rat cDNAs exhibit a high degree of sequence similarity within the SR-BII C-terminal domain (62-67% identity when compared with the human sequence), suggesting that this variant is biologically important. SR-BII protein represents approximately 12% of the total immunodetectable SR-BI/II protein in mouse liver. Subcellular fractionation of transfected Chinese hamster ovary cells showed that SR-BII, like SR-BI, is enriched in caveolae, indicating that the altered cytoplasmic tail does not affect targeting of the receptor. SR-BII mediated both selective cellular uptake of cholesteryl ether from HDL as well as HDL-dependent cholesterol efflux from cells, although with approximately 4-fold lower efficiency than SR-BI. In vivo studies using adenoviral vectors showed that SR-BII was relatively less efficient than SR-BI in reducing plasma HDL cholesterol. These studies show that SR-BII, an HDL receptor isoform containing a distinctly different cytoplasmic tail, mediates selective lipid transfer between HDL and cells, but with a lower efficiency than the previously characterized variant.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Alternative Splicing / genetics
  • Amino Acid Sequence
  • Animals
  • CD36 Antigens / chemistry*
  • CHO Cells
  • Carrier Proteins*
  • Cholesterol / pharmacokinetics
  • Cholesterol Esters / metabolism
  • Cricetinae
  • Lipid Metabolism*
  • Lipoproteins, HDL / metabolism*
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Proteins*
  • Mice
  • Molecular Sequence Data
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins*
  • Receptors, Lipoprotein / metabolism*
  • Receptors, Scavenger
  • Scavenger Receptors, Class B
  • Sialoglycoproteins*
  • Transfection / genetics

Substances

  • CD36 Antigens
  • Carrier Proteins
  • Cholesterol Esters
  • Lipoproteins, HDL
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • SCARB2 protein, human
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Sialoglycoproteins
  • high density lipoprotein receptors
  • high density lipoprotein binding protein
  • Cholesterol