ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux.
ATP-binding cassette transporter 1 (ABCA1), the defective transporter in Tangier disease, binds and promotes cellular cholesterol and phospholipid efflux to apolipoprotein I (apoA-I). Based on a high degree of sequence homology between ABCA1 and ABCA7, a transporter of unknown function, we investigated the possibility that ABCA7 might be involved in apolipoprotein binding and lipid efflux. Similarly to cells expressing ABCA1, HEK293 cells overexpressing ABCA7 showed specific binding and cross-linking of lipid-poor apoA-I. ABCA7 expression increased cellular phosphatidylcholine and sphingomyelin efflux to apoA-I in a manner similar to ABCA1 but had no effect on cholesterol efflux. Western analysis showed a high protein level of ABCA7 in mouse spleen, lung, adrenal, and brain but low expression in liver. In contrast to ABCA1, ABCA7 showed moderate basal mRNA and protein levels in macrophages and lymphocytes but no induction by liver X receptor activation. These studies show that ABCA7 has the ability to bind apolipoproteins and promote efflux of cellular phospholipids without cholesterol, and they suggest a possible role of ABCA7 in cellular phospholipid metabolism in peripheral tissues.
Wang
Nan
N
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA. nw30@columbia.edu
Lan
Debin
D
Gerbod-Giannone
Marie
M
Linsel-Nitschke
Patrick
P
Jehle
Andreas Werner
AW
Chen
Wengen
W
Martinez
Laurent O
LO
Tall
Alan R
AR
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology*; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D008168:Lung / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D057093:Orphan Nuclear Receptors; D010537:Peritoneum / Q000473:pathology; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters; C485856:Abca7 protein, mouse; D016632:Apolipoprotein A-I; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010713:Phosphatidylcholines; D010743:Phospholipids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013109:Sphingomyelins; D002784:Cholesterol