Lysophosphatidylcholine export by human ABCA7

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1862; no. 7; pp. 658 - 665
• Main Authors: Tomioka, Maiko, Toda, Yoshinobu, Mañucat, Noralyn B., Akatsu, Hiroyasu, Fukumoto, Manabu, Kono, Nozomu, Arai, Hiroyuki, Kioka, Noriyuki, Ueda, Kazumitsu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2017
• Subjects: ABC proteins; ABC transporters; ABCA1; ABCA7; Alzheimer disease; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Apolipoprotein A-I - metabolism; Apolipoproteins E - metabolism; ATP Binding Cassette Transporter 1 - metabolism; ATP-Binding Cassette Transporters - metabolism; Biological Transport - physiology; cell biology; Cell Line; cerebral cortex; cholesterol; Cholesterol - metabolism; choline; Cricetinae; HEK293 Cells; Humans; immunohistochemistry; Lipid Metabolism - physiology; liquid chromatography; Lysophosphatidylcholine; Lysophosphatidylcholines - metabolism; neuroglia; neurons; pathogenesis; Phosphatidylcholines - metabolism; Phosphatidylethanolamines - metabolism; Phospholipids - metabolism; sphingomyelins; Sphingomyelins - metabolism; tandem mass spectrometry; LpE; ABCA1; APP; ABC; AD; PS; BHK; LC/MS/MS; apoE; ABCA7; Lysophosphatidylcholine; HEK; GFP; Aβ; BSA; DMEM; HDL; PC; ABC proteins; PE; SM; PL; Alzheimer's disease; apoA-I
• ISSN: 1388-1981; 1879-2618; 1879-2618
• DOI: 10.1016/j.bbalip.2017.03.012

The ATP-binding cassette transporter A7 (ABCA7), which is highly expressed in the brain, is associated with the pathogenesis of Alzheimer's disease (AD). However, the physiological function of ABCA7 and its transport substrates remain unclear. Immunohistochemical analyses of human brain sections from AD and non-AD subjects revealed that ABCA7 is expressed in neuron and microglia cells in the cerebral cortex. The transport substrates and acceptors were identified in BHK/ABCA7 cells and compared with those of ABCA1. Like ABCA1, ABCA7 exported choline phospholipids in the presence of apoA-I and apoE; however, unlike ABCA1, cholesterol efflux was marginal. Lipid efflux by ABCA7 was saturated by 5μg/ml apoA-I and was not dependent on apoE isoforms, whereas efflux by ABCA1 was dependent on apoA-I up to 20μg/ml and apoE isoforms. Liquid chromatography–tandem mass spectrometry analyses revealed that the two proteins had different preferences for phospholipid export: ABCA7 preferred phosphatidylcholine (PC)≥lysoPC>sphingomyelin (SM)=phosphatidylethanolamine (PE), whereas ABCA1 preferred PC>>SM>PE=lysoPC. The major difference in the pattern of lipid peaks between ABCA7 and ABCA1 was the high lysoPC/PC ratio of ABCA7. These results suggest that lysoPC is one of the major transport substrates for ABCA7 and that lysoPC export may be a physiologically important function of ABCA7 in the brain. [Display omitted] •ABCA7 and ABCA1 export lipids in the presence of apolipoprotein (apo) A-I and apo E.•The major difference in the pattern of exported lipids between ABCA7 and ABCA1 is the lysoPC/PC ratio of ABCA7.•LysoPC export by ABCA7 may be an important physiological function of ABCA7 in the brain.