Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release.
ABCA7 is expressed predominantly in myelo-lymphatic tissues or reticuloendothelial cells. Physiological role and function of this protein are not fully understood. We isolated the full-length cDNA (type I) and a splicing variant cDNA (type II) of human ABCA7, and developed monoclonal antibodies against extracellular domain (ECD)1 of ABCA7. RT-PCR experiments suggested that human ABCA7 gene produced the type II mRNA in a tissue-specific manner. Immunostaining revealed that the type I ABCA7, expressed in HEK293 cells, was localized to the plasma membrane and ECD1 was exposed to the extracellular space as was the case for ABCA1. HEK293 cells expressing type I ABCA7 showed apoA-I-dependent cholesterol and phospholipid release. In contrast, type II ABCA7 appeared to be localized mainly in endoplasmic reticulum and did not show apoA-I-dependent cholesterol and phospholipid release. Alternative splicing could be involved in the post-transcriptional regulation of the expression and function of human ABCA7.
Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Yuika
Y
Ikeda
Sumiko
S
Abe-Dohmae
Youichi
Y
Munehira
Ryo
R
Aoki
Shinobu
S
Kawamoto
Akiko
A
Furuya
Kenya
K
Shitara
Teruo
T
Amachi
Noriyuki
N
Kioka
Michinori
M
Matsuo
Shinji
S
Yokoyama
Kazumitsu
K
Ueda
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D050356:Lipid Metabolism; D010743:Phospholipids / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000502:physiology
C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D010743:Phospholipids; D012333:RNA, Messenger; D002784:Cholesterol