MURINE SR-BI, A HIGH-DENSITY-LIPOPROTEIN RECEPTOR THAT MEDIATES SELECTIVE LIPID UPTAKE, IS N-GLYCOSYLATED AND FATTY ACYLATED AND COLOCALIZES WITH PLASMA-MEMBRANE CAVEOLAE

The class B, type I scavenger receptor, SR-BI, was the first molecular ly well defined cell surface high density lipoprotein (HDL) receptor t o be described, It mediates transfer of lipid from HDL to cells via se lective lipid uptake, a mechanism distinct from receptor-mediated endo cytosis via clathrin-coated pits and vesicles, SR-BI is expressed most abundantly in steroidogenic tissues (adrenal gland, ovary), where tro phic hormones coordinately regulate its expression with steroidogenesi s, and in the liver, where it may participate in reverse cholesterol t ransport, Here we have used immunochemical methods to study the struct ure and subcellular localization of murine SR-BI (mSR-BI) expressed ei ther in transfected Chinese hamster ovary cells or in murine adreno co rtical Y1-BS1 cells, mSR-BI, an similar to 82-kDa glycoprotein, was in itially synthesized with multiple high mannose N-linked oligosaccharid e chains, and some, but not all, of these were processed to complex fo rms during maturation of the protein in the Golgi apparatus, Metabolic labeling with [H-3]palmitate and [H-3]myristate demonstrated that mSR -BI was fatty acylated, a property shared with CD36, another class B s cavenger receptor, and other proteins that concentrate in specialized, cholesterol- and glycolipid-rich plasma membrane microdomains called caveolae. OptiPrep density gradient fractionation of plasma membranes established that mSR-BI copurified with caveolin-1, a constituent of c aveolae; and immunofluorescence microscopy demonstrated that mSR-BI co localized with caveolin-1 in punctate microdomains across the surface of cells and on the edges of cells, Thus, mSR-BI colocalizes with cave olae, and this raises the possibility that the unique properties of th ese specialized cell surface domains may play a critical role in SR EI mediated transfer of lipids between lipoproteins and cells.