SR-BI-mediated HDL Cholesteryl Ester Delivery in the Adrenal Gland

In adrenocortical cells, scavenger receptor class B, type I (SR-BI) is localized in specialized plasma membrane compartments, called microvillar channels, that retain high density lipoprotein particles (HDL) and are sites for the selective uptake of cholesteryl esters (CE). Formation of microvillar channels is regulated by adrenocorticotropic hormone (ACTH) and requires SR-BI expression. Subsequent to SR-BI-mediated delivery to the plasma membrane, HDL-CE is metabolized to free cholesterol by hormone sensitive lipase and transported to the mitochondria for steroid synthesis via START domain proteins. The relevance of SR-BI to adrenal steroidogenesis is evident by the impairment of glucocorticoid-mediated stress response in the absence of SR-BI-mediated HDL-CE uptake in mice. On the molecular level, SR-BI mediates HDL-CE selective uptake by forming a hydrophobic channel. In addition, SR-BI facilitates bi-directional flux of cholesterol by modifying the phospholipid content of the plasma membrane. SR-BI most likely accomplishes these functions by forming homo-oligomers in the plasma membrane. Examination of SR-BI oligomerization using fluorescence resonance energy transfer spectroscopy revealed that SR-BI multimerizes via its C-terminal region. Overall, SR-BI is the cell surface receptor responsible for selective uptake of lipoprotein cholesterol and its ultimate delivery to sites of hormone synthesis in steroidogenic tissues.