ABC (
ATP-binding cassette)
proteins actively transport a wide variety of substrates, including
peptides,
amino acids,
sugars, metals, drugs,
vitamins and
lipids, across extracellular and intracellular membranes. Of the 49 hum an ABC
proteins, a significant number are known to mediate the extrusion of
lipids from membranes or the flipping of
membrane lipids across the bilayer to generate and maintain
membrane lipid asymmetry. Typical
lipid substrates include
phospholipids,
sterols,
sphingolipids,
bile acids and related
lipid conjugates. Members of the ABCA subfamily of
ABC transporters and other ABC
proteins such as ABCB4, ABCG1 and ABCG5/8 implicated in
lipid transport play important roles in diverse biological processes such as cell signalling,
membrane lipid asymmetry, removal of potentially toxic compounds and metabolites, and apoptosis. The importance of these ABC
lipid transporters in cell physiology is evident from the finding that mutations in the genes encoding many of these
proteins are responsible for severe inherited diseases. For example, mutations in ABCA1 cause
Tangier disease associated with defective efflux of
cholesterol and
phosphatidylcholine from the plasma membrane to the
lipid acceptor
protein apoA1 (
apolipoprotein AI), mutations in ABCA3 cause neonatal
surfactant deficiency associated with a loss in secretion of the
lipid pulmonary surfactants from lungs of newborns, mutations in ABCA4 cause
Stargardt macular degeneration, a
retinal degenerative disease linked to the reduced clearance of
retinoid compounds from photoreceptor cells, mutations in ABCA12 cause harlequin and
lamellar ichthyosis,
skin diseases associated with defective
lipid trafficking in keratinocytes, and mutations in ABCB4 and ABCG5/ABCG8 are responsible for progressive intrafamilial hepatic disease and sitosterolaemia associated with defective
phospholipid and
sterol transport respectively. This chapter highlights the involvement of various mammalian
ABC transporters in
lipid transport in the context of their role in cell signalling, cellular homoeostasis, apoptosis and inherited disorders.