title: SR-BII, an isoform of the scavenger receptor BI containing an alternate cytoplasmic tail, mediates lipid transfer between high density lipoprotein and cells.
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.
authors.affiliation: Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Webb
authors.forename: P M
authors.initials: PM
authors.lastname: Connell
authors.forename: G A
authors.initials: GA
authors.lastname: Graf
authors.forename: E J
authors.initials: EJ
authors.lastname: Smart
authors.forename: W J
authors.initials: WJ
authors.lastname: de Villiers
authors.forename: F C
authors.initials: FC
authors.lastname: de Beer
authors.forename: D R
authors.initials: DR
authors.lastname: van der Westhuyzen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D018955:CD36 Antigens / Q000737:chemistry*; D016466:CHO Cells; D002352:Carrier Proteins; D002784:Cholesterol / Q000493:pharmacokinetics; D002788:Cholesterol Esters / Q000378:metabolism; D006224:Cricetinae; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins; D014162:Transfection / Q000235:genetics
chemical_list: D018955:CD36 Antigens; D002352:Carrier Proteins; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D002784:Cholesterol