PMID- 26695502 OWN - NLM STAT- MEDLINE DCOM- 20160603 LR - 20181202 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 36 IP - 2 DP - 2016 Feb TI - Identification of an Amino Acid Residue Critical for Plasma Membrane Localization of ATP-Binding Cassette Transporter G1--Brief Report. PG - 253-5 LID - 10.1161/ATVBAHA.115.306592 [doi] AB - 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. CI - (c) 2015 American Heart Association, Inc. FAU - Gu, Hong-mei AU - Gu HM AD - 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.). FAU - Wang, Faqi AU - Wang F AD - 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.). FAU - Alabi, Adekunle AU - Alabi A AD - 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.). FAU - Deng, Shijun AU - Deng S AD - 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.). FAU - Qin, Shucun AU - Qin S AD - 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.). FAU - Zhang, Da-wei AU - Zhang DW AD - 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. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151222 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (ABCG1 protein, human) RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Lipoproteins) RN - 97C5T2UQ7J (Cholesterol) RN - GMW67QNF9C (Leucine) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/genetics/*metabolism MH - Amino Acid Substitution MH - Animals MH - Cell Membrane/*metabolism MH - Cholesterol/*metabolism MH - Genotype MH - HEK293 Cells MH - Humans MH - Leucine MH - Lipoproteins/genetics/*metabolism MH - Mice MH - Microscopy, Confocal MH - Mutation MH - Phenotype MH - Transfection OTO - NOTNLM OT - ATP-binding cassette transporter G1 OT - cholesterol efflux OT - lipoprotein OT - mutation OT - protein trafficking EDAT- 2015/12/24 06:00 MHDA- 2016/06/04 06:00 CRDT- 2015/12/24 06:00 PHST- 2015/09/15 00:00 [received] PHST- 2015/12/13 00:00 [accepted] PHST- 2015/12/24 06:00 [entrez] PHST- 2015/12/24 06:00 [pubmed] PHST- 2016/06/04 06:00 [medline] AID - ATVBAHA.115.306592 [pii] AID - 10.1161/ATVBAHA.115.306592 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):253-5. doi: 10.1161/ATVBAHA.115.306592. Epub 2015 Dec 22.