Although studies in recombinant cells indicate that scavenger receptor class B, type I (SR-BI) can promote cholesterol efflux, investigations in transgenic mice overexpressing or deficient in SR-BI endorse its physiological function as selectively sequestering cholesteryl esters from high-density lipoproteins (HDLs). Less clear is the role of SR-BII, a splice variant of the SR-B gene that differs only in the C-terminal cytoplasmic domain. Here, we identify several putative signalling motifs in the C-terminus of human SR-BII, which are absent from SR-BI, and hypothesize that these motifs interact with signalling molecules to mobilize stored cholesteryl esters and/or promote the efflux of intracellular free cholesterol. ‘Pull-down’ assays using a panel of tagged SH3 (Src homology 3) domains showed that cytoplasmic SR-BII, but not cytoplasmic SR-BI, bound the SH3 domain of phospholipase C-γ1; this interaction was not, however, detected under more physiological conditions. Specific anti-peptide antisera identified SR-BII in human monocyte/macrophage THP-1 cells and, in recombinant cells, revealed receptor localization to caveolae, a plasma membrane microdomain that concentrates signal-transducer molecules and acts as a conduit for cholesterol flux between cells and lipoproteins. Consistent with its caveolar localization, expression of human SR-BII in recombinant Chinese hamster ovary cells (CHO–SR-BII) was associated with increased HDL-mediated cholesterol efflux. Nevertheless, when CHO-SR-BII cells were pre-loaded with cholesteryl [3H]oleate and incubated with HDL, cholesteryl ester stores were not reduced compared with control cells. We conclude that although human SR-BII is expressed by macrophages, contains cytoplasmic signalling motifs and localizes to caveolae, its ability to stimulate cholesterol efflux does not reflect enhanced hydrolysis of stored cholesteryl esters.
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Research Article| February 01 2004
Human scavenger receptor class B type II (SR-BII) and cellular cholesterol efflux
Jane V. MULCAHY ;
Dave R. RIDDELL ;
James S. OWEN
James S. OWEN 2
Department of Medicine, Royal Free and University College Medical School, University College London, Royal Free Campus, London NW3 2PF, U.K.
2To whom correspondence should be addressed (e-mail firstname.lastname@example.org).
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Jane V. MULCAHY, Dave R. RIDDELL, James S. OWEN; Human scavenger receptor class B type II (SR-BII) and cellular cholesterol efflux. Biochem J 1 February 2004; 377 (3): 741–747. doi: https://doi.org/10.1042/bj20030307
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