Skip to main content
SpringerLink
Log in

The role of vesicular transport in ABCA1-dependent lipid efflux and its connection with NPC pathways

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

The membrane transporter ATP-binding cassette transporter A1 (ABCA1) has been shown to be the rate-limiting step in the initial formation of plasma high-density lipoprotein (HDL) particles. The mechanisms of action of ABCA1, including its role in the vesicular transport of lipids to the cell surface for the lipidation of HDL apolipoproteins, are not fully understood. Niemann–Pick type C (NPC) disease is most often caused by mutations in the NPC1 gene, whose protein product is believed to facilitate the egress of cholesterol and other lipids from late endosomes and lysosomes to other cellular compartments. This report reviews current knowledge regarding the role of ABCA1 in vesicular lipid transport mechanisms required for HDL particle formation, and the relationship between ABCA1 and NPC1 in this process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

HDL:

high-density lipoprotein

ABCA1:

ATP-binding cassette transporterA1

ApoA-I:

apolipoprotein A-I

NPC:

Niemann–Pick type C

PL:

phospholipids

C:

cholesterol

ER:

endoplasmic reticulum

TGN:

trans-Golgi network

References

  1. Luciani MF, Denizot F, Savary S, Mattei MG, Chimini G (1994) Cloning of two novel ABC transporters mapping on human chromosome 9. Genomics 21:150–159

    Article  PubMed  CAS  Google Scholar 

  2. Dean M, Hamon Y, Chimini G (2001) The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 42:1007–1017

    PubMed  CAS  Google Scholar 

  3. Walter M, Gerdes U, Seedorf U, Assmann G (1994) The high density lipoprotein- and apolipoprotein A-I-induced mobilization of cellular cholesterol is impaired in fibroblasts from Tangier disease subjects. Biochem Biophys Res Commun 205:850–856

    Article  PubMed  CAS  Google Scholar 

  4. Francis GA, Knopp RH, Oram JF (1995) Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier Disease. J Clin Invest 96:78–87

    Article  PubMed  CAS  Google Scholar 

  5. Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, Yu L, Brewer C, Collins JA, Molhuizen HO, Loubser O, Ouelette BF, Fichter K, Ashbourne-Excoffon KJ, Sensen CW, Scherer S, Mott S, Denis M, Martindale D, Frohlich J, Morgan K, Koop B, Pimstone S, Kastelein JJ, Hayden MR et al (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 22:336–345

    Article  PubMed  CAS  Google Scholar 

  6. Bodzioch M, Orso E, Klucken J, Langmann T, Bottcher A, Diederich W, Drobnik W, Barlage S, Buchler C, Porsch-Ozcurumez M, Kaminski WE, Hahmann HW, Oette K, Rothe G, Aslanidis C, Lackner KJ, Schmitz G (1999) The gene encoding ATPbinding cassette transporter 1 is mutated in Tangier disease. Nat Genet 22:347–351

    Article  PubMed  CAS  Google Scholar 

  7. Rust S, Rosier M, Funke H, Real J, Amoura Z, Piette JC, Deleuze JF, Brewer HB, Duverger N, Denefle P, Assmann G (1999) Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet 22:352–355

    Article  PubMed  CAS  Google Scholar 

  8. Lawn RM, Wade DP, Garvin MR, Wang X, Schwartz K, Porter JG, Seilhamer JJ, Vaughan AM, Oram JF (1999) The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest 104:R25–R31

    Article  PubMed  CAS  Google Scholar 

  9. Oram JF (2002) ATP-binding cassette transporter A1 and cholesterol trafficking. Curr Opin Lipidol 13:373–381

    Article  PubMed  CAS  Google Scholar 

  10. Walker JE, Saraste M, Runswick MJ, Gay NJ (1982) Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1:945–951

    PubMed  CAS  Google Scholar 

  11. Langmann T, Klucken J, Reil M, Liebisch G, Luciani MF, Chimini G, Kaminski WE, Schmitz G (1999) Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages. Biochem Biophys Res Commun 257:29–33

    Article  PubMed  CAS  Google Scholar 

  12. Lawn RM, Wade DP, Couse TL, Wilcox JN (2001) Localization of human ATP-binding cassette transporter 1 (ABC1) in normal and atherosclerotic tissues. Arterioscler Thromb Vasc Biol 21:378–385

    PubMed  CAS  Google Scholar 

  13. Wellington CL, Walker EK, Suarez A, Kwok A, Bissada N, Singaraja R, Yang YZ, Zhang LH, James E, Wilson JE, Francone O, McManus BM, Hayden MR (2002) ABCA1 mRNA and protein distribution patterns predict multiple different roles and levels of regulation. Lab Invest 82:273–283

    PubMed  CAS  Google Scholar 

  14. Costet P, Luo Y, Wang N, Tall AR (2000) Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem 275:28240–28245

    PubMed  CAS  Google Scholar 

  15. Schwartz K, Lawn RM, Wade DP (2000) ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR. Biochem Biophys Res Commun 274:794–802

    Article  PubMed  CAS  Google Scholar 

  16. Arakawa R, Yokoyama S (2002) Helical apolipoproteins stabilize ATP-binding cassette transporter A1 by protecting it from thiol protease-mediated degradation. J Biol Chem 277:22426–22429

    Article  PubMed  CAS  Google Scholar 

  17. Wang N, Chen W, Linsel-Nitschke P, Martinez LO, Agerholm-Larsen B, Silver DL, Tall AR (2003) A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-I. J Clin Invest 111:99–107

    Article  PubMed  CAS  Google Scholar 

  18. Martinez LO, Agerholm-Larsen B, Wang N, Chen W, Tall AR (2003) Phosphorylation of a pest sequence in ABCA1 promotes calpain degradation and is reversed by ApoA-I. J Biol Chem 278:37368–37374

    Article  PubMed  CAS  Google Scholar 

  19. See RH, Caday-Malcolm RA, Singaraja RR, Zhou S, Silverston A, Huber MT, Moran J, James ER, Janoo R, Savill JM, Rigot V, Zhang LH, Wang M, Chimini G, Wellington CL, Tafuri SR, Hayden MR (2002) Protein kinase A site-specific phosphorylation regulates ATP-binding cassette A1 (ABCA1)-mediated phospholipid efflux. J Biol Chem 277:41835–41842

    Article  PubMed  CAS  Google Scholar 

  20. Haidar B, Denis M, Krimbou L, Marcil M, Genest J Jr (2002) cAMP induces ABCA1 phosphorylation activity and promotes cholesterol efflux from fibroblasts. J Lipid Res 43:2087–2094

    Article  PubMed  CAS  Google Scholar 

  21. Yamauchi Y, Hayashi M, AbeDohmae S, Yokoyama S (2003) Apolipoprotein A-I activates protein kinase C alpha signaling to phosphorylate and stabilize ATP binding cassette transporter A1 for the high density lipoprotein assembly. J Biol Chem 278:47890–47897

    Article  PubMed  CAS  Google Scholar 

  22. Tang C, Vaughan AM, Oram JF (2004) Janus kinase 2 modulates the apolipoprotein interactions with ABCA1 required for removing cellular cholesterol. J Biol Chem 279:7622–7628

    Article  PubMed  CAS  Google Scholar 

  23. Roosbeek S, Peelman F, Verhee A, Labeur C, Caster H, Lensink MF, Cirulli C, Grooten J, Cochet C, Vandekerckhove J, Amoresano A, Chimini G, Tavernier J, Rosseneu M (2004) Phosphorylation by protein kinase CK2 modulates the activity of the ATP binding cassette A1 transporter. J Biol Chem 279:37779–37788

    Article  PubMed  CAS  Google Scholar 

  24. Hamon Y, Broccardo C, Chambenoit O, Luciani MF, Toti F, Chaslin S, Freyssinet JM, Devaux PF, McNeish J, Marguet D, Chimini G (2000) ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2:399–406

    Article  PubMed  CAS  Google Scholar 

  25. Wang N, Silver DL, Costet P, Tall AR (2000) Specific binding of ApoA-I, enhanced cholesterol efflux, and altered plasma membrane morphology in cells expressing ABC1. J Biol Chem 275:33053–33058

    Article  PubMed  CAS  Google Scholar 

  26. Oram JF, Lawn RM, Garvin MR, Wade DP (2000) ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophages. J Biol Chem 275:34508–34511

    Article  PubMed  CAS  Google Scholar 

  27. Fitzgerald ML, Morris AL, Rhee JS, Andersson LP, Mendez AJ, Freeman MW (2002) Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I. J Biol Chem 277:33178–33187

    Article  PubMed  CAS  Google Scholar 

  28. Denis M, Haidar B, Marcil M, Bouvier M, Krimbou L, Genest J Jr (2004) Molecular and cellular physiology of apolipoprotein A-I lipidation by the ATP-binding cassette transporter A1 (ABCA1). J Biol Chem 279:7384–7394

    Article  PubMed  CAS  Google Scholar 

  29. Wang N, Lan D, Gerbod-Giannone M, Linsel-Nitschke P, Jehle AW, Chen W, Martinez LO, Tall AR (2003) ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. J Biol Chem 278:42906–42912

    Article  PubMed  CAS  Google Scholar 

  30. Abe-Dohmae S, Ikeda Y, Matsuo M, Hayashi M, Okuhira K, Ueda K, Yokoyama S (2004) Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein. J Biol Chem 279:604–611

    Article  PubMed  CAS  Google Scholar 

  31. Remaley AT, Stonik JA, Demosky SJ, Neufeld EB, Bocharov AV, Vishnyakova TG, Eggerman TL, Patterson AP, Duverger NJ, Santamarina-Fojo S, Brewer HB Jr (2001) Apolipoprotein specificity for lipid efflux by the human ABCAI transporter. Biochem Biophys Res Commun 280:818–823

    Article  PubMed  CAS  Google Scholar 

  32. Fitzgerald ML, Mendez AJ, Moore KJ, Andersson LP, Panjeton HA, Freeman MW (2001) ATP-binding cassette transporter A1 contains an NH2-terminal signal anchor sequence that translocates the protein’s first hydrophilic domain to the exoplasmic space. J Biol Chem 276:15137–151345

    PubMed  CAS  Google Scholar 

  33. Orso E, Broccardo C, Kaminski WE, Bottcher A, Liebisch G, Drobnik W, Gotz A, Chambenoit O, Diederich W, Langmann T, Spruss T, Luciani MF, Rothe G, Lackner KJ, Chimini G, Schmitz G (2000) Transport of lipids from Golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice. Nat Genet 24:192–196

    Article  PubMed  CAS  Google Scholar 

  34. Neufeld EB, Remaley AT, Demosky SJ, Stonik JA, Cooney AM, Comly M, Dwyer NK, Zhang M, Blanchette-Mackie J, Santamarina-Fojo S, Brewer HB Jr (2001) Cellular localization and trafficking of the human ABCA1 transporter. J Biol Chem 276:27584–27590

    Article  PubMed  CAS  Google Scholar 

  35. Chen W, Wang N, Tall AR (2005) A PEST deletion mutant of ABCA1 shows impaired internalization and defective cholesterol efflux from late endosomes. J Biol Chem 280:29277–29281

    Article  PubMed  CAS  Google Scholar 

  36. Takahashi Y, Smith JD (1999) Cholesterol efflux to apolipoprotein AI involves endocytosis and resecretion in a calcium-dependent pathway. Proc Natl Acad Sci U S A 96:11358–11363

    Article  PubMed  CAS  Google Scholar 

  37. Smith JD, Waelde C, Horwitz A, Zheng P (2002) Evaluation of the role of phosphatidylserine translocase activity in ABCA1-mediated lipid efflux. J Biol Chem 277:17797–17803

    Article  PubMed  CAS  Google Scholar 

  38. Santamarina-Fojo S, Remaley AT, Neufeld EB, Brewer HB Jr (2001) Regulation and intracellular trafficking of the ABCA1 transporter. J Lipid Res 42:1339–1345

    PubMed  CAS  Google Scholar 

  39. Robenek H, Schmitz G (1991) Abnormal processing of Golgi elements and lysosomes in Tangier disease. Arterioscler Thromb 11:1007–1020

    PubMed  CAS  Google Scholar 

  40. Mendez AJ, Uint L (1996) Apolipoprotein-mediated cellular cholesterol and phospholipid efflux depend on a functional Golgi apparatus. J Lipid Res 37:2510–2524

    PubMed  CAS  Google Scholar 

  41. Remaley AT, Schumacher UK, Stonik JA, Farsi BD, Nazih H, Brewer HB Jr (1997) Decreased reverse cholesterol transport from Tangier disease fibroblasts. Acceptor specificity and effect of brefeldin on lipid efflux. Arterioscler Thromb Vasc Biol 17:1813–1821

    PubMed  CAS  Google Scholar 

  42. Neufeld EB, Stonik JA, Demosky SJ Jr, Knapper CL, Combs CA, Cooney A, Comly M, Dwyer N, Blanchette-Mackie J, Remaley AT, Santamarina-Fojo S, Brewer HB Jr (2004) The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease. J Biol Chem 279:15571–15578

    Article  PubMed  CAS  Google Scholar 

  43. Zha X, Gauthier A, Genest J, McPherson R (2003) Secretory vesicular transport from the Golgi is altered during ATP-binding cassette protein A1 (ABCA1)-mediated cholesterol efflux. J Biol Chem 278:10002–10005

    Article  PubMed  CAS  Google Scholar 

  44. Oram JF, Yokoyama S (1996) Apolipoprotein-mediated removal of cellular cholesterol and phospholipids. J Lipid Res 37:2473–2491

    PubMed  CAS  Google Scholar 

  45. Bared SM, Buechler C, Boettcher A, Dayoub R, Sigruener A, Grandl M, Rudolph C, Dada A, Schmitz G (2004) Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells. Mol Biol Cell 15:5399–5407

    Article  PubMed  CAS  Google Scholar 

  46. Engel T, Lueken A, Bode G, Hobohm U, Lorkowski S, Schlueter B, Rust S, Cullen P, Pech M, Assmann G, Seedorf U (2004) ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export. FEBS Lett 566:241–246

    Article  PubMed  CAS  Google Scholar 

  47. Meiner VL, Cases S, Myers HM, Sande ER, Bellosta S, Schambelan M, Pitas RE, McGuire J, Herz J, Farese RV Jr (1996) Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: evidence suggesting multiple cholesterol esterification enzymes in mammals. Proc Natl Acad Sci U S A 93:14041–14046

    Article  PubMed  CAS  Google Scholar 

  48. Pentchev PG, Brady RO, Blanchette-Mackie EJ, Vanier MT, Carstea ED, Parker CC, Goldin E, Roff CF (1994) The Niemann–Pick C lesion and its relationship to the intracellular distribution and utilization of LDL cholesterol. Biochim Biophys Acta 1225:235–243

    PubMed  CAS  Google Scholar 

  49. Vanier MT, Rodriguez-Lafrasse C, Rousson R, Gazzah N, Juge MC, Pentchev PG, Revol A, Louisot P (1991) Type C Niemann–Pick disease: spectrum of phenotypic variation in disruption of intracellular LDL-derived cholesterol processing. Biochim Biophys Acta 1096:328–337

    PubMed  CAS  Google Scholar 

  50. Coxey RA, Pentchev PG, Campbell G, Blanchette-Mackie EJ (1993) Differential accumulation of cholesterol in Golgi compartments of normal and Niemann–Pick type C fibroblasts incubated with LDL: a cytochemical freeze-fracture study. J Lipid Res 34:1165–1176

    PubMed  CAS  Google Scholar 

  51. Patterson MC, Vanier MT, Suzuki K, Morris JE, Carstea ED, Neufeld EB, Blanchette-Mackie EJ, Pentchev PG (2001) Niemann–Pick Disease Type C: a lipid trafficking disorder. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic & molecular bases of inherited disease. McGraw-Hill, New York, pp 3611–3633

    Google Scholar 

  52. Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, Blanchette-Mackie EJ, Dwyer NK, Neufeld EB, Chang TY, Liscum L, Tagle DA et al (1997) Niemann–Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277:228–231

    Article  PubMed  CAS  Google Scholar 

  53. Loftus SK, Morris JA, Carstea ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, Pentchev PG, Pavan WJ (1997) Murine model of Niemann–Pick C disease: mutation in a cholesterol homeostasis gene. Science 277:232–235

    Article  PubMed  CAS  Google Scholar 

  54. Davies JP, Chen FW, Ioannou YA (2000) Transmembrane molecular pump activity of Niemann–Pick C1 protein. Science 290:2295–2298

    Article  PubMed  CAS  Google Scholar 

  55. Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP (2004) Niemann–Pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science 303:1201–1204

    Article  PubMed  CAS  Google Scholar 

  56. Tseng TT, Gratwick KS, Kollman J, Park D, Nies DH, Goffeau A, Saier MH Jr (1999) The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins. J Mol Microbiol Biotechnol 1:107–125

    PubMed  CAS  Google Scholar 

  57. Higgins ME, Davies JP, Chen FW, Ioannou YA (1999) Niemann–Pick C1 is a late endosome-resident protein that transiently associates with lysosomes and the trans-Golgi network. Mol Genet Metab 68:1–13

    Article  PubMed  CAS  Google Scholar 

  58. Blanchette-Mackie EJ (2000) Intracellular cholesterol trafficking: role of the NPC1 protein. Biochim Biophys Acta 1486:171–183

    PubMed  CAS  Google Scholar 

  59. Naureckiene S, Sleat DE, Lackland H, Fensom A, Vanier MT, Wattiaux R, Jadot M, Lobel P (2000) Identification of HE1 as the second gene of Niemann–Pick C disease. Science 290:2298–2301

    Article  PubMed  CAS  Google Scholar 

  60. Amigo L, Mendoza H, Castro J, Quinones V, Miquel JF, Zanlungo S (2002) Relevance of Niemann–Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice. Hepatology 36:819–828

    PubMed  CAS  Google Scholar 

  61. Garver WS, Heidenreich RA, Erickson RP, Thomas MA, Wilson JM (2000) Localization of the murine Niemann–Pick C1 protein to two distinct intracellular compartments. J Lipid Res 41:673–687

    PubMed  CAS  Google Scholar 

  62. Neufeld EB, Wastney M, Patel S, Suresh S, Cooney AM, Dwyer NK, Roff CF, Ohno K, Morris JA, Carstea ED, Incardona JP, Strauss JF III, Vanier MT, Patterson MC, Brady RO, Pentchev PG, Blanchette-Mackie EJ (1999) The Niemann–Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo. J Biol Chem 274:9627–9635

    Article  PubMed  CAS  Google Scholar 

  63. Patel SC, Suresh S, Kumar U, Hu CY, Cooney A, Blanchette-Mackie EJ, Neufeld EB, Patel RC, Brady RO, Patel YC, Pentchev PG, Ong WY (1999) Localization of Niemann–Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann–Pick type C disease. Proc Natl Acad Sci U S A 96:1657–1662

    Article  PubMed  CAS  Google Scholar 

  64. Holtta-Vuori M, Maatta J, Ullrich O, Kuismanen E, Ikonen E (2000) Mobilization of late-endosomal cholesterol is inhibited by Rab guanine nucleotide dissociation inhibitor. Curr Biol 10:95–98

    Article  PubMed  CAS  Google Scholar 

  65. Zhang M, Dwyer NK, Neufeld EB, Love DC, Cooney A, Comly M, Patel S, Watari H, Strauss JF III, Pentchev PG, Hanover JA, Blanchette-Mackie EJ (2001) Sterol-modulated glycolipid sorting occurs in Niemann–Pick C1 late endosomes. J Biol Chem 276:3417–3425

    Article  PubMed  CAS  Google Scholar 

  66. Zhang M, Sun M, Dwyer NK, Comly ME, Patel SC, Sundaram R, Hanover JA, Blanchette-Mackie EJ (2003) Differential trafficking of the Niemann–Pick C1 and 2 proteins highlights distinct roles in late endocytic lipid trafficking. Acta Paediatr Suppl 92:63–73; discussion 45

    Google Scholar 

  67. Ohgami N, Ko DC, Thomas M, Scott MP, Chang CC, Chang TY (2004) Binding between the Niemann–Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain. Proc Natl Acad Sci U S A 101:12473–12478

    Article  PubMed  CAS  Google Scholar 

  68. Strauss JF III, Liu P, Christenson LK, Watari H (2002) Sterols and intracellular vesicular trafficking: lessons from the study of NPC1. Steroids 67:947–951

    Article  PubMed  CAS  Google Scholar 

  69. Kirchhoff C, Osterhoff C, Young L (1996) Molecular cloning and characterization of HE1, a major secretory protein of the human epididymis. Biol Reprod 54:847–856

    Article  PubMed  CAS  Google Scholar 

  70. Chikh K, Vey S, Simonot C, Vanier MT, Millat G (2004) Niemann–Pick type C disease: importance of N-glycosylation sites for function and cellular location of the NPC2 protein. Mol Genet Metab 83:220–230

    Article  PubMed  CAS  Google Scholar 

  71. Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, BlanchetteMackie EJ, Dwyer NK, Neufeld EB, Chang TY, Liscum L, Strauss JF III, Ohno K, Zeigler M, Carmi R, Sokol J, Markie D, O’Neill RR, van Diggelen OP, Elleder M, Patterson MC, Brady RO, Vanier MT, Pentchev PG, Tagle DA (1997) Niemann–Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277:228–231

    Article  PubMed  CAS  Google Scholar 

  72. Pentchev PG, Comly ME, Kruth HS, Vanier MT, Wenger DA, Patel S, Brady RO (1985) A defect in cholesterol esterification in Niemann–Pick disease (type C) patients. Proc Natl Acad Sci U S A 82:8247–8251

    Article  PubMed  CAS  Google Scholar 

  73. Pentchev PG, Comly ME, Kruth HS, Tokoro T, Butler J, Sokol J, Filling-Katz M, Quirk JM, Marshall DC, Patel S, Vanier MT, Brady RO (1987) Group C Niemann–Pick disease: faulty regulation of low-density lipoprotein uptake and cholesterol storage in cultured fibroblasts. FASEB J 1:40–45

    PubMed  CAS  Google Scholar 

  74. Sleat DE, Wiseman JA, El-Banna M, Price SM, Verot L, Shen MM, Tint GS, Vanier MT, Walkley SU, Lobel P (2004) Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci U S A 101:5886–5891

    Article  PubMed  CAS  Google Scholar 

  75. Ioannou YA (2000) The structure and function of the Niemann–Pick C1 protein. Mol Genet Metab 71:175–181

    Article  PubMed  CAS  Google Scholar 

  76. Liscum L, Faust JR (1987) Low density lipoprotein (LDL)-mediated suppression of cholesterol synthesis and LDL uptake is defective in Niemann–Pick type C fibroblasts. J Biol Chem 262:17002–17008

    PubMed  CAS  Google Scholar 

  77. Choi HY, Karten B, Chan T, Vance JE, Greer WL, Heidenreich RA, Garver WS, Francis GA (2003) Impaired ABCA1-dependent lipid efflux and hypoalphalipoproteinemia in human Niemann–Pick type C disease. J Biol Chem 278:32569–32577

    Article  PubMed  CAS  Google Scholar 

  78. Clee SM, Kastelein JJ, van Dam M, Marcil M, Roomp K, Zwarts KY, Collins JA, Roelants R, Tamasawa N, Stulc T, Suda T, Ceska R, Boucher B, Rondeau C, DeSouich C, Brooks-Wilson A, Molhuizen HO, Frohlich J, Genest J Jr, Hayden MR (2000) Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes. J Clin Invest 106:1263–1270

    Article  PubMed  CAS  Google Scholar 

  79. Xie C, Turley SD, Dietschy JM (1999) Cholesterol accumulation in tissues of the Niemann–Pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ. Proc Natl Acad Sci U S A 96:11992–11997

    Article  PubMed  CAS  Google Scholar 

  80. Chen W, Sun Y, Welch C, Gorelik A, Leventhal AR, Tabas I, Tall AR (2001) Preferential ATP-binding cassette transporter A1-mediated cholesterol efflux from late endosomes/lysosomes. J Biol Chem 276:43564–43569

    Article  PubMed  CAS  Google Scholar 

  81. Feng B, Tabas I (2002) ABCA1-mediated cholesterol efflux is defective in free cholesterolloaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity. J Biol Chem 277:43271–43280

    Article  PubMed  CAS  Google Scholar 

  82. Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, Marks AR, Ron D, Tabas I (2003) The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5:781–792

    Article  PubMed  CAS  Google Scholar 

  83. Feng B, Zhang D, Kuriakose G, Devlin CM, Kockx M, Tabas I (2003) Niemann–Pick C heterozygosity confers resistance to lesional necrosis and macrophage apoptosis in murine atherosclerosis. Proc Natl Acad Sci U S A 100:10423–10428

    Article  PubMed  CAS  Google Scholar 

  84. Lange Y, Ye J, Rigney M, Steck T (2000) Cholesterol movement in Niemann–Pick type C cells and in cells treated with amphiphiles. J Biol Chem 275:17468–17475

    Article  PubMed  CAS  Google Scholar 

  85. Frolov A, Zielinski SE, Crowley JR, DudleyRucker N, Schaffer JE, Ory DS (2003) NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols. J Biol Chem 278:25517–255125

    Article  PubMed  CAS  Google Scholar 

  86. Prinz W (2002) Cholesterol trafficking in the secretory and endocytic systems. Semin Cell Dev Biol 13:197–203

    Article  PubMed  CAS  Google Scholar 

  87. Soccio RE, Breslow JL (2004) Intracellular cholesterol transport. Arterioscler Thromb Vasc Biol 24:1150–1160

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by CIHR operating grant MOP-12660. The authors thank Drs. William Garver and John Oram for helpful discussions. This work was supported by a CIHR/HSFC/Pfizer Canada Training Fellowship in Stroke, Cardiovascular, Obesity, Lipid, and Atherosclerosis Research (SCOLAR) to E. Boadu. G.A. Francis is a Senior Scholar of the Alberta Heritage Foundation for Medical Research.

Author information

Authors and Affiliations

  1. CIHR Group in Molecular and Cell Biology of Lipids, Departments of Medicine and Biochemistry, University of Alberta, Edmonton, AB, Canada, T6G 2S2

    Emmanuel Boadu & Gordon A. Francis

Authors
  1. Emmanuel Boadu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gordon A. Francis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gordon A. Francis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boadu, E., Francis, G.A. The role of vesicular transport in ABCA1-dependent lipid efflux and its connection with NPC pathways. J Mol Med 84, 266–275 (2006). https://doi.org/10.1007/s00109-005-0001-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-005-0001-9

Keywords

Search

Navigation