ABCA1 plays a major role in HDL metabolism.Cholesterol secretion by ABCA1 is dependent on the presence of extracellular acceptors, such as lipid-free apolipoprotein A-I (apoA-I).However, the importance of the direct interaction between apoA-I and ABCA1 in HDL formation remains unclear.In contrast, ABCB4 mediates the secretion of phospholipids and cholesterol in the presence of sodium taurocholate (NaTC) but not in the presence of apoA-I.
In this read more study, we analyzed apoA-I binding and NaTC-dependent lipid efflux by ABCA1.ABCA1 mediated the efflux of cholesterol and phospholipids in the presence of NaTC as well as in the presence of apoA-I in an ATP-dependent manner.The Tangier disease mutation W590S, which resides in the extracellular domain and impairs apoA-I-dependent lipid efflux, greatly decreased NaTC-dependent cholesterol and phospholipid efflux.However, the W590S mutation did not impair apoA-I binding and, conversely, retarded the dissociation of red pygmy dogwood apoA-I from ABCA1.
These results suggest that the W590S mutation impairs ATP-dependent lipid translocation and that lipid translocation or possibly lipid loading, facilitates apoA-I dissociation from ABCA1.NaTC is a good tool for analyzing ABCA1-mediated lipid efflux and allows dissection of the steps of HDL formation by ABCA1.