Role of ABC transporters in lipid transport and human disease

Almost half of the 48 human ATP-binding cassette (ABC) transporter proteins are thought to facilitate the ATP-dependent translocation of lipids or lipid-related compounds. Such substrates include cholesterol, plant sterols, bile acids, phospholipids, and sphingolipids. Mutations in a substantial number of the 48 human ABC transporters have been linked to human disease. Indeed the finding that 12 diseases have been associated with abnormal lipid transport and/or homeostasis demonstrates the importance of this family of transporters in cell physiology. This review highlights the role of ABC transporters in lipid transport and movement, in addition to discussing their roles in cellular homeostasis and inherited disorders.

[1]  K. Ueda,et al.  Formation of Two Intramolecular Disulfide Bonds Is Necessary for ApoA-I-dependent Cholesterol Efflux Mediated by ABCA1* , 2009, Journal of Biological Chemistry.

[2]  R. Dawson,et al.  Structure of a bacterial multidrug ABC transporter , 2006, Nature.

[3]  T. Graham,et al.  Linking phospholipid flippases to vesicle-mediated protein transport. , 2009, Biochimica et biophysica acta.

[4]  P. Nissen,et al.  P-type ATPases. , 2011, Annual review of biophysics.

[5]  W. Davis.  The ATP-binding cassette transporter-2 (ABCA2) increases endogenous amyloid precursor protein expression and Aβ fragment generation. , 2010, Current Alzheimer research.

[6]  K. Ueda,et al.  Lipid outward translocation by ABC proteins , 2010, FEBS letters.

[7]  E. Génin,et al.  ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease , 2005, Neurobiology of Disease.

[8]  F. Quiocho,et al.  Crystal structure of a catalytic intermediate of the maltose transporter , 2007, Nature.

[9]  Yue Weng,et al.  Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding , 2009, Science.

[10]  J. Oram,et al.  The cell cholesterol exporter ABCA1 as a protector from cardiovascular disease and diabetes. , 2009, Biochimica et biophysica acta.

[11]  G. Meer.  Dynamic Transbilayer Lipid Asymmetry , 2011 .

[12]  Jonathan C. Cohen,et al.  Expression of ABCG5 and ABCG8 Is Required for Regulation of Biliary Cholesterol Secretion* , 2005, Journal of Biological Chemistry.

[13]  Yoshiyuki Kubo,et al.  ABCA5 Resides in Lysosomes, and ABCA5 Knockout Mice Develop Lysosomal Disease-Like Symptoms , 2005, Molecular and Cellular Biology.

[14]  P. Edwards,et al.  Pleiotropic roles of bile acids in metabolism. , 2013, Cell metabolism.

[15]  B. Hagenbuch,et al.  OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies , 2012, British journal of pharmacology.

[16]  W. Davis.  The ATP-binding cassette transporter-2 (ABCA2) regulates cholesterol homeostasis and low-density lipoprotein receptor metabolism in N2a neuroblastoma cells. , 2011, Biochimica et biophysica acta.

[17]  A. M. George,et al.  Perspectives on the structure-function of ABC transporters: the Switch and Constant Contact models. , 2012, Progress in biophysics and molecular biology.

[18]  Jonathan C. Cohen,et al.  High-level expression of ABCG5 and ABCG8 attenuates diet-induced hypercholesterolemia and atherosclerosis in Ldlr−/− mice Published, JLR Papers in Press, June 1, 2004. DOI 10.1194/jlr.M400167-JLR200 , 2004, Journal of Lipid Research.

[19]  A. Fischer,et al.  Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy. , 2012, Methods in Enzymology.

[20]  P. Krajcsi,et al.  Utilization of membrane vesicle preparations to study drug–ABC transporter interactions , 2008, Expert opinion on drug metabolism & toxicology.

[21]  Jonathan C. Cohen,et al.  Purification and reconstitution of sterol transfer by native mouse ABCG5 and ABCG8. , 2008, Biochemistry.

[22]  Douglas C. Rees,et al.  The E. coli BtuCD Structure: A Framework for ABC Transporter Architecture and Mechanism , 2002, Science.

[23]  H. Saito,et al.  Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles* , 2007, Journal of Biological Chemistry.

[24]  B. Sikic,et al.  Molecular Pathways: Regulation and Therapeutic Implications of Multidrug Resistance , 2012, Clinical Cancer Research.

[25]  C. Scott,et al.  Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport, reduced protease regulation and skin-barrier dysfunction , 2012, Cell and Tissue Research.

[26]  Gerhard F. Ecker,et al.  Computational models for prediction of interactions with ABC-transporters. , 2008, Drug discovery today.

[27]  F. Goñi,et al.  Transbilayer (flip‐flop) lipid motion and lipid scrambling in membranes , 2010, FEBS letters.

[28]  C. Ackerley,et al.  Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[29]  N. C. Roy,et al.  Multidrug resistance gene deficient (mdr1a–/–) mice have an altered caecal microbiota that precedes the onset of intestinal inflammation , 2009, Journal of applied microbiology.

[30]  A. Tall,et al.  LXR-Induced Redistribution of ABCG1 to Plasma Membrane in Macrophages Enhances Cholesterol Mass Efflux to HDL , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[31]  Shannon M. Conley,et al.  DNA nanoparticle-mediated ABCA4 delivery rescues Stargardt dystrophy in mice. , 2012, The Journal of clinical investigation.

[32]  B. de Kruijff,et al.  The transbilayer movement of phosphatidylcholine in vesicles reconstituted with intrinsic proteins from the human erythrocyte membrane. , 1980, Biochimica et biophysica acta.

[33]  D. Rees,et al.  An Inward-Facing Conformation of a Putative Metal-Chelate-Type ABC Transporter , 2007, Science.

[34]  S. Biswas,et al.  Retinoid Binding Properties of Nucleotide Binding Domain 1 of the Stargardt Disease-associated ATP Binding Cassette (ABC) Transporter, ABCA4* , 2012, The Journal of Biological Chemistry.

[35]  D. Rader,et al.  Pathways by Which Reconstituted High-Density Lipoprotein Mobilizes Free Cholesterol From Whole Body and From Macrophages , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[36]  N. Grishin,et al.  Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. , 2000, Science.

[37]  P. Edwards,et al.  Dancing with the sterols: critical roles for ABCG1, ABCA1, miRNAs, and nuclear and cell surface receptors in controlling cellular sterol homeostasis. , 2012, Biochimica et biophysica acta.

[38]  D. Kelsell,et al.  Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. , 2011, Archives of dermatology.

[39]  G. Schmitz,et al.  Complete coding sequence, promoter region, and genomic structure of the human ABCA2 gene and evidence for sterol-dependent regulation in macrophages. , 2001, Biochemical and biophysical research communications.

[40]  T. Graham,et al.  Phospholipid flippases: building asymmetric membranes and transport vesicles. , 2012, Biochimica et biophysica acta.

[41]  A. Herrmann,et al.  Function of prokaryotic and eukaryotic ABC proteins in lipid transport. , 2005, Biochimica et biophysica acta.

[42]  E. Tarling.  Expanding roles of ABCG1 and sterol transport , 2013, Current opinion in lipidology.

[43]  P. Edwards,et al.  ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter , 2011, Proceedings of the National Academy of Sciences.

[44]  K. Tew,et al.  Identification of a novel first exon of the human ABCA2 transporter gene encoding a unique N-terminus. , 2004, Biochimica et biophysica acta.

[45]  E. Masliah,et al.  Alzheimer's disease: recent advances and future perspectives. , 2012, Journal of Alzheimer's disease : JAD.

[46]  M. Fitzgerald,et al.  ABC transporters, atherosclerosis and inflammation. , 2010, Atherosclerosis.

[47]  F. Theodoulou,et al.  Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance , 2011, British journal of pharmacology.

[48]  F. Lammert,et al.  Spontaneous cholecysto‐ and hepatolithiasis in Mdr2−/− mice: A model for low phospholipid‐associated cholelithiasis , 2004, Hepatology.

[49]  Paul T. Tarr,et al.  ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and regulate cholesterol homeostasis through SREBP-2 Published, JLR Papers in Press, October 4, 2007. , 2008, Journal of Lipid Research.

[50]  Geoffrey Chang,et al.  Flexibility in the ABC transporter MsbA: Alternating access with a twist , 2007, Proceedings of the National Academy of Sciences.

[51]  J. R. McMillan,et al.  Localization of ABCA12 from Golgi apparatus to lamellar granules in human upper epidermal keratinocytes , 2007, Experimental dermatology.

[52]  E. Shoubridge,et al.  Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism , 2012, Nature Genetics.

[53]  F. Van Bambeke,et al.  ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions. , 2011, Current drug targets.

[54]  D. Rees,et al.  The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation , 2008, Science.

[55]  K. Palczewski,et al.  The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease. , 2010, Advances in experimental medicine and biology.

[56]  S. Grinstein,et al.  The distribution and function of phosphatidylserine in cellular membranes. , 2010, Annual review of biophysics.

[57]  Susan E Wert,et al.  Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. , 2010, Annual review of medicine.

[58]  A. M. George,et al.  Mechanism of the ABC transporter ATPase domains: catalytic models and the biochemical and biophysical record , 2013, Critical reviews in biochemistry and molecular biology.

[59]  K. Ueda,et al.  Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1s⃞ Published, JLR Papers in Press, May 15, 2006. , 2006, Journal of Lipid Research.

[60]  A. Bush,et al.  ABCA3 transporter deficiency. , 2012, American journal of respiratory and critical care medicine.

[61]  K. Locher,et al.  Structural Basis of Trans-Inhibition in a Molybdate/Tungstate ABC Transporter , 2008, Science.

[62]  K. Linton,et al.  Canalicular ABC transporters and liver disease , 2012, The Journal of pathology.

[63]  K. Locher,et al.  Structure of an ABC transporter in complex with its binding protein , 2007, Nature.

[64]  A. Menon,et al.  Reconstitution of Glucosylceramide Flip-Flop across Endoplasmic Reticulum , 2012, The Journal of Biological Chemistry.

[65]  U. Brinkmann,et al.  Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[66]  S. Kemp,et al.  See Blockindiscussions, Blockinstats, Blockinand Blockinauthor Blockinprofiles Blockinfor Blockinthis Blockinpublication X-linked Blockinadrenoleukodystrophy: Blockinclinical, Metabolic, Blockingenetic Blockinand Blockinpathophysiological Aspects Article Blockin Blockinin Blockin Blockinbiochimica B , 2022 .

[67]  M. Hohl,et al.  Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation , 2012, Nature Structural &Molecular Biology.

[68]  S. Colowick,et al.  Methods in Enzymology , Vol , 1966 .