title: Lysophosphatidylcholine export by human ABCA7.
abstract: 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.
authors.affiliation: Institute for integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Tomioka
authors.affiliation: Faculty of Health Care, Tenri Health Care University, Tenri, Nara 632-0018, Japan. Electronic address: toda@tenriyorozu-u.ac.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Toda
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Noralyn B
authors.initials: NB
authors.lastname: Mañucat
authors.affiliation: Graduate School of Medical Sciences and Medical School, Nagoya City University, Nagoya 467-8601, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Institute for integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8502, Japan; Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
authors.affiliation: Institute for integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8502, Japan; Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. Electronic address: uedak@kais.kyoto-u.ac.jp.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D057809:HEK293 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: C411895:ABCA7 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D013109:Sphingomyelins; C483858:phosphatidylethanolamine; D002784:Cholesterol
keywords: ABC proteins; ABCA1; ABCA7; Alzheimer's disease; Lysophosphatidylcholine