The ABCA1 transporter and ApoA-I: obligate or facultative partners?
Premature cardiovascular disease, the leading cause of death in the Western world, is frequently associated with disorders of lipid metabolism and, in particular, with low levels of circulating high-density lipoprotein (HDL) cholesterol. However, the relationship among HDL, centripetal cholesterol transport, and early atherogenesis has remained elusive until the characterization of the molecular defect leading to Tangier disease. In this disorder, the loss of function of the adenosine triphosphate-binding cassette transporter, ABCA1, leads to an impaired formation of nascent HDL particles by preventing the release of cellular lipids and cholesterol to the acceptor apolipoprotein (apo)A-I. Lipids bound to circulating apoA-I are derived from cell membranes via active effluxes experimentally elicited by the interaction of nascent lipid-free apoA-I with the membrane itself. The nature of this key interaction is still enigmatic, however, and a large number of controversial results (discussed in this article) have been reported. Indeed, although the active mechanism that assists the extraction of cellular lipids entails as a simplest option the existence of a dedicated receptor at the membrane, the unambiguous identification of this molecule has not been achieved. This lack of precise evidence makes it necessary to consider alternative models, taking into account the dynamic and functional constraints that regulate the interaction between apoA-I and the plasma membrane.
Marguet
Didier
D
Center of Immunology-INSERM/CNRS-at Marseille Luminy, France.
Chimini
Giovanna
G
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D013631:Tangier Disease / Q000378:metabolism / Q000503:physiopathology
D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008563:Membrane Lipids