Roles of scavenger receptor BI and apo A-I in selective uptake of HDL cholesterol by adrenal cells

Adrenal cells obtain cholesterol for steroid production via the selective uptake of cholesteryl ester (CE) from HDL particles, a process in which CE is transferred to the plasma membrane without degradation of the HDL particle. Although this process has been studied for two decades, only recently have the receptor and the HDL ligand been identified. Scavenger class B, type I, (SR-BI) is regulated by ACTH in adrenocortical cells in parallel with steroid production. Antibody to SR-BI blocks the uptake and utilization of HDL CE for steroid production in YI-BSI adrenal cells. The adrenal glands of SR-BI knockout mice are depleted in cholesterol providing complementary evidence that SR-BI is responsible for HDL CE accumulation in adrenal cells. SR-BI-mediated HDL CE selective uptake is a two-step process in which SR-BI first interacts with multiple sites in apoA-I with the amphipathic For All -helical repeat units of apoA-I serving as recognition motifs. This is followed by efficient CE transfer down its concentration gradient to the plasma membrane, a process requiring the extracellular domain of SR-BI. Other scavenger receptors bind HDL but do not afford the CE transfer step. Adrenal glands from apoA-I knockout mice lack CE stores, indicating that apoAI is essential for HDL selective uptake in vivo. ApoA-I knockout HDL particles bind normally to SR-BI but do not permit efficient CE transfer to the cell. These findings suggest that apoA-I has an important role in the transfer of HDL CE that goes beyond its function as a ligand for interaction with SR-BI.