Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release

Ikeda, Yuika; Abe-Dohmae, Sumiko; Munehira, Youichi; Aoki, Ryo; Kawamoto, Shinobu; Furuya, Akiko; Shitara, Kenya; Amachi, Teruo; Kioka, Noriyuki; Matsuo, Masaru; Yokoyama, Shinji; Ueda, Kazumitsu

doi:10.1016/j.bbrc.2003.10.002

Cited by 72 publications

(98 citation statements)

References 23 publications

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“…This discrepancy may be explained if ABCA7 rapidly turns over in the surface. An exon 5 splicing variant of ABCA7 was found to remain intracellularly ( 27 ), but the primers and antibody employed in the current study for detection of ABCA7 mRNA and protein do not differentiate the variant. The current fi ndings with ABCA7 is very similar to ABCA1, stabilized against its calpain-mediated degradation by helical apolipoproteins when the HDL biogenesis reaction is ongoing ( 26,28,29 ), perhaps forming a complex prior to the endocytotic internalization for its intracellular proteolysis to recycle ABCA1 to the cell surface ( 24 ).…”

Section: Resultsmentioning

confidence: 71%

Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7

Tanaka

Abe-Dohmae

Iwamoto

et al. 2010

Journal of Lipid Research

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Section: Resultsmentioning

confidence: 71%

Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7

Tanaka

Abe-Dohmae

Iwamoto

et al. 2010

Journal of Lipid Research

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“…An alternative splicing event for ABCA7 has been described, resulting in the generation of two ABCA7 transcripts with different tissue distribution and subcellular localization (plasma membrane or endoplasmic reticulum) [19]. Whether this splicing event is of physiological relevance is yet unknown.…”

Section: Abca7mentioning

confidence: 99%

The ABCA subfamily—gene and protein structures, functions and associated hereditary diseases

Albrecht¹,

Viturro²

2006

Pflugers Arch - Eur J Physiol

106

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To date, 12 members of the human ABCA subfamily are identified. They share a high degree of sequence conservation and have been mostly related with lipid trafficking in a wide range of body locations. Mutations in some of these genes have been described to cause severe hereditary diseases related with lipid transport, such as fatal surfactant deficiency or harlequin ichthyosis. In addition, most of them are hypothesized to participate in the subcellular sequestration of drugs, thereby being responsible for the resistance of several carcinoma cell lines against drug treatment. The objective of this review is to summarize the literature for this subfamily of ABC transporter proteins, excluding ABCA1 and ABCA4, which will be discussed in other chapters of this issue.

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“…Recent demographic studies have shown a decrease in incidences in developed countries most likely due to improved treatment and prevention of vascular risk factors 2, 3, 4. Genome‐wide association studies (GWAS) have revealed novel molecular pathways, among these the ATP‐binding‐cassette transporter A7 ( ABCA7 ),5, 6 which may be involved in both transmembrane lipid transport and phagocytosis of amyloid‐ β in the brain 7, 8, 9, 10, 11, 12, 13, 14. Following these GWAS findings, rare loss‐of‐function variants in ABCA7 were reported to confer risk of Alzheimer's disease in case–control studies in Icelandic and Belgian populations 15, 16.…”

Section: Introductionmentioning

confidence: 99%

“…ABCA7 is highly expressed in brain tissue,9, 21, 22 most abundant in microglia and oligodendrocytes 7, 23. Previous studies comparing ABCA7 knock‐out mice with wild‐type mice or J20 amyloidogenic mice demonstrate that ABCA7 is involved in clearance of amyloid‐ β in the brain through phagocytosis 12, 24.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies comparing ABCA7 knock‐out mice with wild‐type mice or J20 amyloidogenic mice demonstrate that ABCA7 is involved in clearance of amyloid‐ β in the brain through phagocytosis 12, 24. Furthermore, early studies on ABCA7 explored lipid efflux capacities and suggested that ABCA7 contributes to phospholipid and cholesterol transport 8, 9, 10, 21, 25, 26, 27. Since ABCA7 may be implicated in both Alzheimer's disease pathology and lipid metabolism, studying the impact of common genetic variation in ABCA7 for risk of Alzheimer's disease and other types of dementia, lipid metabolism, ischemic heart disease and ischemic cerebrovascular disease is of interest.…”

Section: Introductionmentioning

confidence: 99%

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ABCA7 and risk of dementia and vascular disease in the Danish population

Kjeldsen

Tybjærg‐Hansen

Nordestgaard

et al. 2017

Ann Clin Transl Neurol

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Objective ATP‐binding‐cassette transporter A7(ABCA7) is suggested to be involved in lipid transport as well as in phagocytosis of amyloid‐β in the brain. We tested the hypothesis that a common genetic variant in ABCA7 is associated with dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels in the general population, independent of the common apolipoprotein E(APOE) genotype.MethodsFor this purpose, we genotyped a common genetic variant in ABCA7, identified in genome‐wide‐association‐studies of Alzheimer's disease, in 104,258 individuals from the Danish general population, and also meta‐analyzed our results with publicly available consortia data.ResultsMultifactorially adjusted hazard ratios for Alzheimer's disease were 1.07 (95% confidence interval:0.93–1.23) and 1.72 (1.24–2.40) for GA and AA versus GG genotype. Results were similar after APOE genotype adjustment and when only APOE ɛ33 carriers were studied. Including 178,304 individuals, the meta‐analyzed odds ratio for Alzheimer's disease per one allele ABCA7 rs4147929 increase was 1.15 (1.12–1.18). ABCA7 genotype was not convincingly associated with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, or with lipid levels. Including 288,563 individuals, meta‐analyzed odds ratios for ischemic heart disease per one allele ABCA7 rs4147929 increase was 1.01 (0.99–1.03).InterpretationA common genetic variant in ABCA7 was associated with high risk of Alzheimer's disease independent of APOE genotype. The lack of association with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels suggests that ABCA7 is not important for atherosclerosis. Thus, our findings support the suggested role of ABCA7 in Alzheimer's disease pathology and phagocytic clearance of amyloid‐β in the brain.

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Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release

Cited by 72 publications

References 23 publications

Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7

Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7

The ABCA subfamily—gene and protein structures, functions and associated hereditary diseases

ABCA7 and risk of dementia and vascular disease in the Danish population

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