Regulation and intracellular trafficking of the ABCA1 transporter.
The discovery of the role of the ATP-binding cassette transporter A1 (ABCA1) in mediating apolipoprotein A-I-mediated efflux has led to a dramatic increase in our knowledge of the molecular mechanisms involved in cholesterol efflux and cellular metabolism. In this review, we discuss several aspects of ABCA1 regulation including i) transcriptional regulation, ii) substrate specificity and availability, iii) accessory proteins, iv) acceptor specificity and availability, and v) protein trafficking. The majority of studies of ABCA1 regulation to date have focused on the identification of promoter elements that determine ABCA1 gene transcription. Here we also review the potential functional role of ABCA1 in reverse cholesterol transport. Given the key role that ABCA1 plays in cholesterol homeostasis, it is likely that there are multiple mechanisms for controlling the overall transporter activity of ABCA1.
Santamarina-Fojo
S
S
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. silvia@mdb.nhlbi.nih.gov
Remaley
A T
AT
Neufeld
E B
EB
Brewer
H B
HB
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D013261:Sterols / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists; D014158:Transcription, Genetic
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D016207:Cytokines; D018160:Receptors, Cytoplasmic and Nuclear; D013261:Sterols; D014157:Transcription Factors; D002784:Cholesterol; D000242:Cyclic AMP