Potential role of ABCA7 in cellular lipid efflux to apoA-I.
ABCA7 is homologous to ABCA1 and has recently been shown in cell culture to bind apolipoprotein A-I (apoA-I) and to promote the efflux of phospholipids. However, it is not known if ABCA7 promotes lipid efflux in vivo. When expressed in HEK293 cells, both human and mouse ABCA7 promoted phospholipid efflux to apoA-I but no detectable cholesterol efflux. However, genetic knockdown of ABCA7 in mouse peritoneal macrophages did not affect phospholipid or cholesterol efflux to apoA-I. Moreover, in ABCA1-knockout macrophages, there was no detectable apoA-I-stimulated phospholipid efflux, inconsistent with a residual role of ABCA7. In contrast to plasma membrane localization of ABCA7 in transfected embryonic kidney cells, immunofluorescence microscopy of endogenous ABCA7 in macrophages showed a predominantly intracellular localization of the protein. Strikingly, immunofluorescence studies of adult mouse kidney revealed an apical brush border membrane localization of ABCA7 in the proximal tubule, suggesting that ABCA7 may come in contact with apoA-I in the glomerular filtrate. Although ABCA7 does not contribute to apolipoprotein-mediated lipid efflux in resting macrophages, its cell surface location in the kidney suggests that it could serve such a role in tissue microenvironments.
Linsel-Nitschke
Patrick
P
Division of Molecular Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA. pl2031@columbia.edu
Jehle
Andreas W
AW
Shan
Jing
J
Cao
Guoqing
G
Bacic
Desa
D
Lan
Debin
D
Wang
Nan
N
Tall
Alan R
AR
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001692:Biological Transport; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000737:chemistry / Q000166:cytology; D050356:Lipid Metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000737:chemistry; D010743:Phospholipids / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D018528:ATP-Binding Cassette Transporters; C485856:Abca7 protein, mouse; D016632:Apolipoprotein A-I; D010743:Phospholipids