Expression and functional characterization of ABCG1 splice variant ABCG1(666)

FEBS Letters - Tập 580 - Trang 4551-4559 - 2006
Thomas Engel1, Guenther Bode1,2, Aloys Lueken1, Markus Knop3, Frank Kannenberg1,2, Jerzy-Roch Nofer1,2, Gerd Assmann1,2, Udo Seedorf1
1Leibniz Institute of Arteriosclerosis Research, Westphalian Wilhelms-University, Domagkstr. 3, 48149 Muenster, Germany
2Institute of Clinical Chemistry and Laboratory Medicine, Westphalian Wilhelms-University, 48149 Muenster, Germany
3Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, Westphalian Wilhelms-University, 48149 Muenster, Germany

Tóm tắt

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.

Tài liệu tham khảo

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FEBS Letters

Tập 580

4551-4559

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