title: Characterization of palmitoylation of ATP binding cassette transporter G1: effect on protein trafficking and function.
abstract: ATP-binding cassette transporter G1 (ABCG1) mediates cholesterol efflux onto lipidated apolipoprotein A-I and HDL and plays a role in various important physiological functions. However, the mechanism by which ABCG1 mediates cholesterol translocation is unclear. Protein palmitoylation regulates many functions of proteins such as ABCA1. Here we investigated if ABCG1 is palmitoylated and the subsequent effects on ABCG1-mediated cholesterol efflux. We demonstrated that ABCG1 is palmitoylated in both human embryonic kidney 293 cells and in mouse macrophage, J774. Five cysteine residues located at positions 26, 150, 311, 390 and 402 in the NH2-terminal cytoplasmic region of ABCG1 were palmitoylated. Removal of palmitoylation at Cys311 by mutating the residue to Ala (C311A) or Ser significantly decreased ABCG1-mediated cholesterol efflux. On the other hand, removal of palmitoylation at sites 26, 150, 390 and 402 had no significant effect. We further demonstrated that mutations of Cys311 affected ABCG1 trafficking from the endoplasmic reticulum. Therefore, our data suggest that palmitoylation plays a critical role in ABCG1-mediated cholesterol efflux through the regulation of trafficking.
authors: Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors: Hong-mei
authors: HM
authors: Gu
authors: Ge
authors: G
authors: Li
authors: Xia
authors: X
authors: Gao
authors: Luc G
authors: LG
authors: Berthiaume
authors: Da-wei
authors: DW
authors: Zhang
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D054878:Lipoylation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
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; D000255:Adenosine Triphosphate; D002784:Cholesterol; D003545:Cysteine