The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex.
Recent work identified ABCA1 as the major regulator of plasma HDL-cholesterol responsible for the removal of excess choline-phospholipids and cholesterol from peripheral cells and tissues. ABCA1 function may depend on the association with heteromeric proteins and to identify these candidates a human liver yeast two-hybrid library was screened with the carboxyterminal 144 amino acids of ABCA1. Beta2-syntrophin was found to interact with ABCA1 and the C-terminal five amino acids of ABCA1 proned to represent a perfect tail for binding to syntrophin PDZ domains. Immunoprecipitation further confirmed the association of ABCA1 and beta2-syntrophin and in addition utrophin, known to couple beta2-syntrophin and its PDZ ligands to the F-actin cytoskeleton, was identified as a constituent of this complex. ABCA1 in the plasmamembrane of human macrophages was found to be partially associated with Lubrol rafts and effluxed choline-phospholipids involve these microdomains. Beta2-syntrophin does not colocalize in these rafts indicating that beta2-syntrophin may participate in the retaining of ABCA1 in cytoplasmic vesicles and for the targeting of ABCA1 to plasmamembrane microdomains when ABCA1 is released from beta2-syntrophin.
Buechler
Christa
C
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany.
Boettcher
Alfred
A
Bared
Salim Maa
SM
Probst
Mario C O
MC
Schmitz
Gerd
G
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D000328:Adult; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D049411:Utrophin
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D003598:Cytoskeletal Proteins; D049029:Dystrophin-Associated Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D049411:Utrophin; C091824:syntrophin