The apolipoprotein E-dependent low density lipoprotein cholesteryl ester selective uptake pathway in murine adrenocortical cells involves chondroitinsulfate proteoglycans and an alpha(2)-macroglobulin receptor

Cells acquire lipoprotein cholesterol by receptor-mediated endocytosis and selective uptake pathways. In the latter case, lipoprotein cholesteryl este r (CE) is transferred to the plasma membrane without endocytosis and degrad ation of the lipoprotein particle. Previous studies with Y1/E/tet/2/3 murin e adrenocortical cells that were engineered to express apolipoprotein (apo) E demonstrated that apoE expression enhances low density lipoprotein (LDL) CE uptake by both selective and: endocytic pathways. The present experimen ts test the hypothesis that apoE-dependent LDL CE selective up take is medi ated by scavenger receptor, class B, type I (SR-BI), Surprisingly, SR-BI ex pression was not detected in the Y1/E/tet/2/3 clone of Y1 adrenocortical ce lls, indicating the presence of a distinct apoE-dependent pathway for LDL C E selective uptake. ApoE-dependent LDL CE selective uptake in Y1/E/tet/2/3 cells was inhibited by receptor-associated protein and by activated alpha ( 2)-macroglobulin (alpha M-2), suggesting the participation of the LDL recep tor-related protein/alpha M-2 receptor. Reagents that inhibited proteoglyca n synthesis or removed cell surface chondroitin sulfate proteoglycan comple tely blocked apoE-dependent LDL CE selective uptake. None of these reagents inhibited SR-BI-mediated LDL CE selective uptake in the Y1-BS1 clone of Y1 cells in which LDL CE selective uptake is mediated by GR-BI. We conclude t hat LDL CE selective uptake in adrenocortical cells occurs via SR-BI-indepe ndent and SR-BI-dependent pathways. The SR-BI-independent pathway is an apo E-dependent process that involves both chondroitin sulfate proteoglycans an d an alpha M-2 receptor.