ABCA1: regulation, trafficking and association with heteromeric proteins.
HDL metabolism is crucial in maintaining cellular cholesterol and phospholipid homeostasis and prevention of atherosclerosis progression. Recent work identified the ATP-binding cassette transporter A1 (ABCA1) as the major regulator of plasma high density lipoprotein (HDL) cholesterol responsible for the removal of excess cholesterol from peripheral cells and tissues. Here we discuss some novel aspects of the ABCA1 network: 1) the cellular pathways involved in cholesterol and phospholipid efflux, 2) regulation of ABCA1, 3) sulfonylurea receptor 1 (SUR1)- or cystic fibrosis transmembrane conductance regulator (CFTR)-like function of ABCA1, 4) interaction of the ABCA1 C-terminus with beta2-syntrophin, 5) ABCA1 modulation of the Rho GTPase Cdc42, 6) localization of ABCA1 in plasma membrane microdomains and intracellular sites, 7) differential effects of prebeta-HDL precursors on ABCA1 mediated alpha-HDL particle formation and 8) ABCA1 in platelets and its relation to phosphatidylserine-flippase activity. A complex regulatory network and additional antiatherogenic features that may depend on the composition of prebeta-HDL precursor particles are believed to coordinate ABCA1 function in reverse cholesterol and phospholipid transport. Distinct prebeta-HDL ligand-specific receptor-clusters are involved that may modulate specific signaling pathways with varying outcomes related to prebeta-HDL particle composition, the cell-type and the cellular response status.
Schmitz
Gerd
G
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany. gerd.schmitz@klinik.uni-regensburg.de
Buechler
Christa
C
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology*; D000209:Acute-Phase Proteins; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology; D002352:Carrier Proteins / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D003920:Diabetes Mellitus / Q000503:physiopathology; D049029:Dystrophin-Associated Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology; D015394:Molecular Structure; D010718:Phosphatidylserines / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D015398:Signal Transduction / Q000502:physiology*; D064233:Sulfonylurea Receptors; D013631:Tangier Disease / Q000503:physiopathology; D000099231:Lipopolysaccharide-Binding Protein
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008076:Cholesterol, HDL; D049029:Dystrophin-Associated Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099231:Lipopolysaccharide-Binding Protein; C577836:ABCA1 protein, human; C577507:ABCC8 protein, human; C091824:syntrophin