Expression and regulation of multiple murine ATP-binding cassette transporter G1 mRNAs/isoforms that stimulate cellular cholesterol efflux to high density lipoprotein.
The murine Abcg1 gene is reported to consist of 15 exons that encode a single mRNA (herein referred to as Abcg1-a) and protein. We now demonstrate that (i) the murine gene contains two additional coding exons downstream of exon 1, (ii) transcription involves the use of multiple promoters, and (iii) the RNA undergoes alternative splicing reactions. As a result, three mRNAs are expressed that encode three putative protein isoforms that differ at their amino terminus. ABCG1 transcripts are induced in vivo in multiple tissues in response to the liver X receptor ligand T0901317. Identification and characterization of four liver X receptor response elements in the intron downstream of exon 2 provides a mechanism by which this induction occurs. Importantly, cholesterol efflux to high density lipoprotein was stimulated following transfection of Hek293 cells with plasmids encoding individual ABCG1 isoforms. In situ hybridization studies in embryonic day 11.5-15.5 mouse embryos revealed strong expression of ABCG1 transcripts in the olfactory epithelium, hind brain, eye, and dorsal root ganglia. The relatively high levels of expression in neuronal tissues and the eye suggest that ABCG1-dependent cholesterol efflux may be critical for normal neuronal function in addition to its role in macrophages.
Nakamura
Kotoka
K
Department of Biological Chemistry and Medicine, University of California, Los Angeles, CA 90095, USA.
Kennedy
Matthew A
MA
Baldán
Angel
A
Bojanic
Dragana D
DD
Lyons
Karen
K
Edwards
Peter A
PA
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002784:Cholesterol / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008074:Lipoproteins / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D000071518:Liver X Receptors; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D020218:Response Elements / Q000502:physiology
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol