抄録
Cholesterol and phopholipids are essential for our body as major components of cell membrane or a material of hormones and bile acid, but the excess cholesterol and lipids are risk factor for arteriosclerosis. Several ATP-binding cassette (ABC) proteins are involved in the transport of phospholipids and sterols. ABCA1 and ABCA7 support apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein. ABCB4 (MDR2) is involved in transporting phosphatidylcholine (PC) into bile to generate micelle with bile acids. ABCG1, one of a half-type ABC proteins and induced by LXR/RXR pathway, is thought to be involved in cholesterol homeostasis. And ABCG5 and ABCG8 genes are mutated in patients sitosterolemia, a disorder involving the accumulation of cholesterol and other sterols. To understand physiological importance of ABC proteins in lipid homeostasis and reveal the mechanism of lipid transport, we established cell lines stably expressing these ABC proteins, and studied their subcellular localization, functions, and post-translational regulations. ABCG1 localizes in plasma membrane in HEK293 cells. Co-immunoprecipitation and cross-linking experiments demonstrated that ABCG1 forms a homodimer, whereas ABCG5 and ABCG8 localize in plasma membrane and functions as heterodimer. Importance and mechanism of lipid transport by ABC proteins will be discussed. [Jpn J Physiol 55 Suppl:S30 (2005)]
