title: Identification of an Amino Acid Residue Critical for Plasma Membrane Localization of ATP-Binding Cassette Transporter G1--Brief Report.
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.
  
  
  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.
authors.affiliation: 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.).
authors.forename: Hong-mei
authors.initials: HM
authors.lastname: Gu
authors.affiliation: 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.).
authors.forename: Faqi
authors.initials: F
authors.lastname: Wang
authors.affiliation: 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.).
authors.forename: Adekunle
authors.initials: A
authors.lastname: Alabi
authors.affiliation: 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.).
authors.forename: Shijun
authors.initials: S
authors.lastname: Deng
authors.affiliation: 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.).
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
authors.affiliation: 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.
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Zhang
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D007930:Leucine; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D009154:Mutation; D010641:Phenotype; D014162:Transfection
chemical_list: C419353:ABCG1 protein, human; C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D002784:Cholesterol; D007930:Leucine
keywords: ATP-binding cassette transporter G1; cholesterol efflux; lipoprotein; mutation; protein trafficking