Identification of an Amino Acid Residue Critical for Plasma Membrane Localization of ATP-Binding Cassette Transporter G1--Brief Report

Hong-mei Gu; Faqi Wang; Adekunle Alabi; Shijun Deng; Shucun Qin; Da-wei Zhang

doi:10.1161/ATVBAHA.115.306592

Identification of an Amino Acid Residue Critical for Plasma Membrane Localization of ATP-Binding Cassette Transporter G1--Brief Report

Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):253-5. doi: 10.1161/ATVBAHA.115.306592. Epub 2015 Dec 22.

Authors

Hong-mei Gu¹, Faqi Wang¹, Adekunle Alabi¹, Shijun Deng¹, Shucun Qin¹, Da-wei Zhang²

Affiliations

¹ From the Departments of Pediatrics and Biochemistry, Group on the Molecular and Cell Biology of Lipids, University of Alberta, Alberta, Canada (H.-M.G., F.W., A.A., S.D., D.-W.Z.); and Institute of Atherosclerosis in Taishan Medical University, Taian, China (S.Q., D.-W.Z.).
² From the Departments of Pediatrics and Biochemistry, Group on the Molecular and Cell Biology of Lipids, University of Alberta, Alberta, Canada (H.-M.G., F.W., A.A., S.D., D.-W.Z.); and Institute of Atherosclerosis in Taishan Medical University, Taian, China (S.Q., D.-W.Z.). dzhang@ualberta.ca.

PMID: 26695502
DOI: 10.1161/ATVBAHA.115.306592

Abstract

Objective: ATP-binding cassette transporter G1 (ABCG1) mediates cholesterol efflux to lipidated lipoproteins. Conflicting data about cellular localization of ABCG1 and its effect on cholesterol efflux have been reported. Here, we investigated the underlying mechanisms for these different observations.

Approach and results: Confocal microscopy and biotinylation were used to assess cell surface localization of ABCG1. We found that mouse ABCG1 (mABCG1) used in one previous study has a substitution of Leu to Pro at position 550 (mG1-L550P). When the corresponding Leu at position 562 in human ABCG1 (hABCG1) was mutated to Pro (hG1-L562P), the mutant hABCG1, like mG1-L550P, mainly resided intracellularly, whereas wild-type mABCG1 and hABCG1 were localized on the plasma membrane. However, replacement of this Leu with Pro had no significant effect on mABCG1- and hABCG1-mediated cholesterol efflux.

Conclusions: Leu at position 550/562 in mABCG1/hABCG1 is critical for their plasma membrane localization but not for ABCG1-mediated cholesterol efflux. Our findings indicate that the substitution of Leu to Pro at position 550 in mABCG1 may contribute to the non-cell surface localization of mABCG1 observed in the previous study.

Keywords: ATP-binding cassette transporter G1; cholesterol efflux; lipoprotein; mutation; protein trafficking.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism*
Amino Acid Substitution
Animals
Cell Membrane / metabolism*
Cholesterol / metabolism*
Genotype
HEK293 Cells
Humans
Leucine
Lipoproteins / genetics
Lipoproteins / metabolism*
Mice
Microscopy, Confocal
Mutation
Phenotype
Transfection

Substances

ABCG1 protein, human
ABCG1 protein, mouse
ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters
Lipoproteins
Cholesterol
Leucine

Grants and funding

Canadian Institutes of Health Research/Canada