SR-BII, AN ISOFORM OF THE SCAVENGER RECEPTOR BI CONTAINING AN ALTERNATE CYTOPLASMIC TAIL, MEDIATES LIPID TRANSFER BETWEEN HIGH-DENSITY-LIPOPROTEIN AND CELLS

The scavenger receptor class B, type I (SR-BI), binds high density lip oprotein (HDL) and mediates selective uptake of cholesteryl ester from HDL and HDL-dependent cholesterol efflux from cells. We recently iden tified a new mRNA variant that differs from the previously characteriz ed form in that the encoded C-terminal cytoplasmic domain is almost co mpletely different. In the present study, we demonstrate that the mRNA s for mouse SR-BI and SR-BII (previously termed SR-BI.2) are the alter natively spliced products of a single gene. The translation products p redicted from human, bovine, mouse, hamster, and rat cDNAs exhibit a h igh degree of sequence similarity within the SR-BII C-terminal domain (62-67% identity when compared with the human sequence), suggesting th at this variant is biologically important. SR-BII protein represents a pproximately 12% of the total immunodetectable SR-BI/II protein in mou se liver. Subcellular fractionation of transfected Chinese hamster ova ry cells showed that SR-BII, like SR-BI, is enriched in caveolae, indi cating that the altered cytoplasmic tail does not affect targeting of the receptor. SR-BII mediated both selective cellular uptake of choles teryl 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 relat ively less efficient than SR-BI in reducing plasma HDL cholesterol, Th ese studies show that SR-BII, an HDL, receptor isoform containing a di stinctly different cytoplasmic tail, mediates selective lipid transfer between HDL and cells, but with a lower efficiency than the previousl y characterized variant.