Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1

摘要: Mutations of the ABC1 transporter have been identified as defect in Tangier disease, characterized by low HDL and cholesterol ester accumulation macrophages. A full-length mouse cDNA was used to investigate mechanisms lipid efflux apoA-I or transfected 293 cells. expression markedly increased cellular phospholipid but had only minor effects on HDL. The appears involve a direct interaction between ABC1, because substantially binding at cell surface, chemical cross-linking immunoprecipitation analysis showed that binds directly ABC1. In contrast scavenger receptor BI (SR-BI), another surface molecule capable facilitating efflux, preferentially bound lipid-free not Immunofluorescence confocal microscopy is primarily localized surface. absence apoA-I, cells overexpressing displayed distinctive morphology, plasma membrane protrusions resembling echinocytes form when there are excess lipids outer hemileaflet. studies provide evidence for HDL, indicating free metabolic substrate Plasma may act phospholipid/cholesterol flippase, providing