title: Molecular mechanisms of subcellular localization of ABCG5 and ABCG8.
abstract: Human ABCG subfamily proteins ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8 are half-type ATP-binding cassette (ABC) proteins that transport sterols or xenobiotics. ABCG1, ABCG2, and ABCG4 function as homodimers on the plasma membrane. In contrast, ABCG5 and ABCG8 function as heterodimers on the plasma membrane, and the homodimer of either ABCG5 or ABCG8 is retained in the endoplasmic reticulum (ER). To examine the molecular mechanisms of the regulated trafficking of ABCG5 and ABCG8, the subcellular localizations of chimeric proteins, fused with ABCG1 or ABCG2, were analyzed. Homodimers of chimeric proteins, in which the N-terminal cytosolic domain of ABCG1 or ABCG2 was fused to the C-terminal transmembrane domain of ABCG5 or ABCG8 localized to the plasma membrane, whereas chimeric proteins in which the N-terminal cytosolic domain of ABCG5 or ABCG8 was fused to the C-terminal transmembrane domain of ABCG1 or ABCG2 localized to the ER. Mutations in ER-retrieval motif-like sequences in ABCG5 or ABCG8 did not affect their subcellular localization. This suggests that the N-terminal cytosolic domains of ABCG5 and ABCG8 are involved in ER retention of their homodimers, and that novel ER-retention or -retrieval motifs exist within these domains.
authors.affiliation: Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirata
authors.forename: Morio
authors.initials: M
authors.lastname: Okabe
authors.forename: Aya
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Michinori
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D011993:Recombinant Fusion Proteins