Expression and functional characterization of ABCG1 splice variant ABCG1(666).
The ATP-binding cassette transporter ABCG1 mediates the transport of excess cholesterol from macrophages and other cell types to high density lipoprotein (HDL) but not to lipid-depleted apolipoprotein AI. Several splice variants which may have different functions have been identified in mammals. In the current study, we characterized the human splice variant ABCG1(666), which differs from full-length ABCG1(678) by absence of an internal segment of 12 amino acids (VKQTKRLKGLRK). Accordingly spliced ABCG1 transcripts were detected in macrophages and liver in approximately twofold higher amounts than the alternatively spliced ABCG1 form encoding full-length ABCG1. We used transient and stable expression of ABCG1(666) fusion proteins to characterize glycosylation, subcellular localization, molecular interaction and functions of this ABCG1 variant. It could be demonstrated that ABCG1(666) is located at the cell surface and has the ability to form cholesterol transport competent homodimers which affect cellular cholesterol export in a similar manner as previously characterized forms of ABCG1. Our results support that ABCG1(666) may in fact be the most prominent form of functional ABCG1 expressed in the human.
Engel
Thomas
T
Leibniz Institute of Arteriosclerosis Research, Westphalian Wilhelms-University, Domagkstr. 3, 48149 Muenster, Germany. engeltho@uni-muenster.de
Bode
Guenther
G
Lueken
Aloys
A
Knop
Markus
M
Kannenberg
Frank
F
Nofer
Jerzy-Roch
JR
Assmann
Gerd
G
Seedorf
Udo
U
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002784:Cholesterol / Q000378:metabolism; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger; D002784:Cholesterol