SR-BI does not require raft/caveola localisation for cholesteryl ester selective uptake in the human adrenal cell line NCI-H295R

Abstract

Class B type I scavenger receptor (SR-BI) mediates the selective uptake of high-density lipoprotein (HDL)-derived cholesteryl esters (HDL-CE) in steroidogenic cells and hepatocytes. SR-BI is enriched in the caveolae of some cell types, genetically modified or not, and these domains have already been shown to constitute primary acceptors for HDL-CE. Nevertheless, the fate of caveola-free cell types has not yet been discussed. NCI-H295R, a human adrenal cell line, highly active in HDL-CE uptake via SR-BI, does not display any morphologically defined caveolae and expresses caveolin at a very low level. Using two different fractionation protocols, we have shown, in this cell type, that SR-BI is homogeneously distributed along the plasma membrane and consists principally of a non-raft membrane-associated pool. Raft destabilisation and caveolin-1 displacement from plasma membrane did not modify the SR-BI-mediated HDL-CE selective uptake. Moreover, the induction of SR-BI expression that is associated with increased CE selective uptake was not associated with any modification in caveolin-1 expression or any raft-targeting mechanism of SR-BI in NCI-H295R. In conclusion, we provide evidence that SR-BI does not require raft/caveola localisation to be implicated in CE selective uptake either in basal or in induced conditions.