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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.

Pubmed ID: 12054535

Authors

  • Buechler C
  • Boettcher A
  • Bared SM
  • Probst MC
  • Schmitz G

Journal

Biochemical and biophysical research communications

Publication Data

May 3, 2002

Associated Grants

None

Mesh Terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Adult
  • Amino Acid Sequence
  • Cell Membrane
  • Cells, Cultured
  • Cytoplasmic Vesicles
  • Cytoskeletal Proteins
  • Dystrophin-Associated Proteins
  • Fibroblasts
  • Humans
  • Macromolecular Substances
  • Membrane Proteins
  • Middle Aged
  • Molecular Sequence Data
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • Utrophin