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Intracellular Cholesterol and Phospholipid Trafficking: Comparable Mechanisms in Macrophages and Neuronal Cells

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Abstract

During the past ten years considerable evidences have accumulated that in addition to monocytes/macrophages, that are implicated in innate immunity and atherogenesis, neuronal cells also exhibit an extensive cellular metabolism. The present study focuses on the major protein players that establish cellular distribution of cholesterol and phospholipids. Evidences are provided that neuronal cells and monocytes/macrophages are equipped with comparable intracellular lipid trafficking mechanisms. Selected examples are presented that trafficking dysfunctions lead to disease development, such as Tangier disease and Niemann-Pick disease type C, or contribute to the pathogenesis of diseases such as Alzheimer disease and atherosclerosis.

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REFERENCES

  1. Cullis, P. R., Fenske, D. B., and Hope, M. J. 1996. Physical properties and functional roles of lipids in membranes. Pages 1–33, in Vance, D. E., and Vance, J. E. (eds.), Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier, Amsterdam.

    Google Scholar 

  2. Voelker, D. R. 1996. Lipid assembly into cell membranes. Pages 391–423, in Vance, D. E., and Vance, J. E. (eds.), Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier, Amsterdam.

    Google Scholar 

  3. Liscum, L. and Munn, N. J. 1999. Intracellular cholesterol transport. Biochim. Biophys. Acta 1438:19–37.

    Google Scholar 

  4. Simons, K. and Ikonen, E. 1997. Functional rafts in cell membranes. Nature 387:569–572.

    Google Scholar 

  5. Ikonen, E. and Parton, R. G. 2000. Caveolins and cellular cholesterol balance. Traffic 1:212–217.

    Google Scholar 

  6. Simons, K. and Toomre, D. 2000. Lipid rafts and signal transduction. Nat. Rev. 1:31–39.

    Google Scholar 

  7. Vance, J. E., Campenot, R. B., and Vance, D. E. 2000. The synthesis and transport of lipids for axonal growth and nerve regeneration. Biochim. Biophys. Acta 1486:84–96.

    Google Scholar 

  8. Röper, K., Corbeil, D., and Huttner, W. B. 2000. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane. Nat. Cell Biol. 2:582–592.

    Google Scholar 

  9. Corbeil, D., Röper, K., Fargeas, C. A., Joester, A., and Huttner, W. B. 2001. Prominin: A story of cholesterol, plasma membrane protrusions and human pathology. Traffic 2:82–91.

    Google Scholar 

  10. Powell, K. S. and Latterich, M. 2000. The making and breaking of the endoplasmic reticulum. Traffic 1:689–694.

    Google Scholar 

  11. Lippincott-Schwartz, J. and Zaal, K. J. 2000. Cell cycle maintenance and biogenesis of the Golgi complex. Histochem. Cell. Biol. 114:93–103.

    Google Scholar 

  12. Griffits, G. 2000. Gut thoughts on the Golgi complex. Traffic 1:738–745.

    Google Scholar 

  13. Davis, R. A. and Vance, J. E. 1996. Structure, assembly and secretion of lipoproteins. Pages 473–493, in Vance, D. E., and Vance, J. E. (eds.), Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier, Amsterdam.

    Google Scholar 

  14. Fielding, P. E. and Fielding, C. J. 1996. Dynamics of lipoprotein transport in the human circulatory system. Pages 495–516, in Vance, D. E., and Vance, J. E. (eds.), Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier, Amsterdam.

    Google Scholar 

  15. Compagnone, N. A. and Mellon, S. H. 2000. Neurosteroids: Biosynthesis and function of these novel neuromodulators. Front. Neuroendocrinol. 21:1–56.

    Google Scholar 

  16. Gagescu, R., Gruenberg, J., and Smythe, E. 2000. Membrane dynamics in endocytosis: Structure-function relationship. Traffic 1:84–88.

    Google Scholar 

  17. Mukherjee, S. and Maxfield, F. R. 2000. Role of membrane organization and membrane domains in endocytic lipid trafficking. Traffic 1:203–211.

    Google Scholar 

  18. Wang, Y., Thiele, C., and Huttner, W. B. 2000. Cholesterol is required for the formation of regulated and constitutive secretory vesicles from the trans-Golgi network. Traffic 1:952–962.

    Google Scholar 

  19. Huijbregts, R. P. H., Topalof, L., and Bankaitis, V. A. 2000. Lipid metabolism and regulation of membrane tarfficking. Traffic 1:195–202.

    Google Scholar 

  20. Hurley, J. H. and Meyer, T. 2001. Subcellular targeting by membrane lipids. Curr. Opin. Cell Biol. 13:146–152.

    Google Scholar 

  21. Schmitz, G., Kaminski, W. E., and Orsó, E. 2000. ABC transporters in cellular lipid trafficking. Curr. Opin. Lipidol. 11:493–501.

    Google Scholar 

  22. Menon, A. K., Watkins, W. E. 3rd, and Hrafnsdottir, S. 2000. Specific proteins are required to translocate phosphatidylcholine bidirectionally across the endoplasmic reticulum. Curr. Biol. 10:241–252.

    Google Scholar 

  23. Khelef, N., Soe, T. T., Quehenberger, O., Beatini, N., Tabas, I., and Maxfield, F. R. 2000. Enrichment of acyl coenzyme A:cholesterol O-acyltransferase near trans-golgi network and endocytic recycling compartment. Arterioscler. Thromb. Vasc. Biol. 20:1769–1776.

    Google Scholar 

  24. Brown, M. S., Goldstein, J. L., Krieger, M., Ho, Y. K., and Anderson, R. G. 1979. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J. Cell Biol. 82:597–613.

    Google Scholar 

  25. Goldstein, J. L., Brown, M. S., Anderson, R. G. W., Russel, D. W., and Schneider, W. J. 1985. Receptor mediated endocytosis: Concepts emerging from the LDL receptor system. Annu. Rev. Cell Biol. 1:1–39.

    Google Scholar 

  26. Kruth, H. S. 2001. Macrophage foam cells and atherosclerosis. Front. Biosci. 6:429–455.

    Google Scholar 

  27. Dietschy, J. M. and Turley, S. D. 2001. Cholesterol metabolism in the brain. Curr. Opin. Lipidol. 12:105–112.

    Google Scholar 

  28. Liu, P. L., Li, W-P., Machleidt, T., and Anderson, R. G. W. 1999. Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells. Nat. Cell Biol. 1:369–375.

    Google Scholar 

  29. Bevers, E. M., Cumfurius, P., Dekkers, D. W. C., and Zwaal, R. F. A. 1999. Lipid translocation across the plasma membrane of mammalian cells. Biochim. Biophys. Acta 1439:317–330.

    Google Scholar 

  30. Van Meer, G. 2000. Cellular organelles: How lipids get there, and back. Trends Cell Biol. 10:550–552.

    Google Scholar 

  31. Chen, C. Y., Ingram, M. F., Rosal, P. H., and Graham, T. R. 1999. Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. J. Cell Biol. 147:1223–1236.

    Google Scholar 

  32. Wiedmer, T., Zhou, Q., Kwoh, D. Y., and Sims, P. J. 2000. Identification of three new members of the phospholipid scramblase gene family. Biochim. Biophys. Acta 1467:244–253.

    Google Scholar 

  33. Ueda, K., Yoshida, A., and Amachi, T. 1999. Recent progress in P-glycoprotein research. Anticancer Drug Res. 14:115–121.

    Google Scholar 

  34. Tessner, T. G. and Stenson, W. F. 2000. Overexpression of MDR1 in an intestinal cell line results in increased cholesterol uptake from micelles. Biochem. Biophys. Res. Commun. 267:565–571.

    Google Scholar 

  35. Lam, F. C., Liu, R., Lu, P., Shapiro, A. B., Renoir, J-M., Sharom, F. J., and Reiner, P. B. 2001. β-amyloid efflux mediated by p-glycoprotein. J. Neurochem. 76:1121–1128.

    Google Scholar 

  36. Klucken, J., Büchler, C., Orsó, E., Kaminski, W. E., PorschÖzcürümez, M., Liebisch, G., Kapinsky, M., Diederich, W., Drobnik, W., Dean, M., Allikmets, R., and Schmitz, G. 2000. ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc. Natl. Acad. Sci. USA 97:817–822.

    Google Scholar 

  37. Brügger, B., Sandhoff, R., Wegehingel, S., Gorgas, K., Malsam, J., Helms, J. B., Lehmann, W. D., Nickel, W., and Wieland, F. T. 2000. Evidence for segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J. Cell Biol. 151:507–518.

    Google Scholar 

  38. Diederich, W., Orsó, E., Drobnik, W., and Schmitz, G. 2001. Apolipoprotein Al and HDL3 inhibit spreading of human monocytes through a mechanism that involves cholesterol depletion and regulation of CDC42. Atherosclerosis (in press).

  39. Ledesma, M. D., Simons, K., and Dotti, C. G. 1998. Neuronal polarity: Essential role of protein-lipid complexes in axonal sorting. Proc. Natl. Acad. Sci. USA 95:3966–3971.

    Google Scholar 

  40. Ledesma, M. D., Brügger, B., Bunning, C., Wieland, F. T., and Dotti, C. G. 1999. Maturation of the axonal plasma membrane requires upregulation of sphingomyelin synthesis and formation of protein-lipid complexes. EMBO J. 18:1761–1771.

    Google Scholar 

  41. Bradke, F. and Dotti, C. G. 2000. Establishment of neuronal polarity: Lessons from cultured hippocampal neurons. Curr. Opin. Neurobiol. 10:574–581.

    Google Scholar 

  42. Jareb, M. and Banker, G. 1997. Inhibition of axonal growth by brefeldin A in hippocampal neurons in culture. J. Neurosci. 17:8955–8963.

    Google Scholar 

  43. Dickson, B. J. 2001. Rho GTPases in growth cone guidance. Curr. Opin. Neurobiol. 11:103–110.

    Google Scholar 

  44. Redmond, L. and Ghosh, A. 2001. The role of Notch and Rho GTPase signaling in the control of dendritic development. Curr. Opin. Neurobiol. 11:111–117.

    Google Scholar 

  45. Hodgkin, M. N., Clark, J. M., Rose, S., Saqib, K., and Wakelam, M. J. 1999. Characterization of the regulation of phospholipase D activity in the detergent-insoluble fraction of HL60 cells by protein kinase C and small G-proteins. Biochem. J. 339:87–93.

    Google Scholar 

  46. Fiucci, G., Czarny, M., Lavie, Y., Zhao, D., Berse, B., Blusztajn, J. K., and Liscovitch, M. 2000. Changes in phospholipase D isoform activity and expression in multidrug-resistant human cancer cells. Int. J. Cancer 85:882–888.

    Google Scholar 

  47. Czarny, M., Fiucci, G., Lavie, Y., Banno, Y., Nozawa, Y., and Liscovitch, M. 2000. Phospholipase D2: Functional interaction with caveolin in low-density membrane microdomains. FEBS Lett. 467:326–332.

    Google Scholar 

  48. Shaul, P. W. and Anderson, R. G. W. 1998. Role of plasmalemmal caveolae in signal transduction. Am. J. Physiol. 275:L843–L851.

    Google Scholar 

  49. Engelman, J. A., Zhang, X. L., Galbiati, F., Volonté, D., Sotgia, F., Pestell, R. G., Minetti, C., Scherer, P. E., Okamoto, T., and Lisanti, M. P. 1998. Molecular genetics of the caveolin gene family: Implications for human cancers, diabetes, Alzheimer disease, and muscular dystrophy. Am. J. Hum. Genet. 63:1578–1587.

    Google Scholar 

  50. Mikol, D. D., Hong, H. L., Cheng, H-L., and Feldman, E. L. 1999. Caveolin-1 expression in Schwann cells. Glia 27:39–52.

    Google Scholar 

  51. Kiss, A. L. and Geuze, H. J. 1997. Caveolae can be alternative endocytic structures in elicited macrophages. Eur. J. Cell Biol. 73:19–27.

    Google Scholar 

  52. Nishiyama, K., Trapp, B. D., Ikezu, T., Ransohoff, R. M., Tomita, T., Iwatsubo, T., Kanazawa, I., Hsiao, K. K., Lisanti, M. P., and Okamoto, T. 1999. Caveolin-3 upregulation activates beta-secretase-mediated cleavage of the amyloid precursor protein in Alzheimer's disease. J. Neurosci. 19:6538–6548.

    Google Scholar 

  53. Lee, S. J., Liyanage, U., Bickel, P. E., Xia, W., Lansbury, P. T., and Kosik, K. S. 1998. A detergent-insoluble membrane compartment contains A-beta in vivo. Nat. Med. 4:730–734.

    Google Scholar 

  54. Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C. G., and Simons, K. 1998. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc. Natl. Acad. Sci. USA 95:6460–6464.

    Google Scholar 

  55. Moebius, F. F., Fitzky, B. U., and Glossmann, H. 2000. Genetic defects in postsqualene cholesterol biosynthesis. Trends Endocrinol. Metab. 11:106–114.

    Google Scholar 

  56. Waterham, H. R. and Wanders, R. J. A. 2000. Biochemical and genetic aspects of 7-dehydrocholesterol reductase and Smith-Lemli-Opitz syndrome. Biochim. Biophys. Acta 1529:340–356.

    Google Scholar 

  57. Herman, G. E. 2000. X-linked dominant disorders of cholesterol biosynthesis in man and mouse. Biochim. Biophys. Acta 1529:357–373.

    Google Scholar 

  58. Edwards, P. A., Tabor, D., Kast, H. R., and Venkateswaran, A. 2000. Regulation of gene expression by SREBP and SCAP. Biochim. Biophys. Acta 1529:103–113.

    Google Scholar 

  59. Nimpf, J. and Schneider, W. J. 2000. From cholesterol transport to signal transduction: Low density lipoprotein receptor, very low density lipoprotein receptor, and apolipoprotein E receptor-2. Biochim. Biophys. Acta 1529:287–298.

    Google Scholar 

  60. Argraves, W. S. 2001. Members of the low density lipoprotein receptor family control diverse physiological processes. Front. Biosci. 6:406–416.

    Google Scholar 

  61. Page, K. J., Hollister, R. D., and Hyman, B. T. 1998. Dissociation of apolipoprotein and apolipoprotein receptor response to lesion in the rat brain: An in situ hybridization study. Neurosci. 85:1161–1171.

    Google Scholar 

  62. Posse de Chaves, E. I., Vance, D. E., Campenot, R. B., Kiss, R. S., and Vance, J. E. 2000. Uptake of lipoproteins for axonal growth of sympathetic neurons. J. Biol. Chem. 275:19883–19890.

    Google Scholar 

  63. Schmitz, G., Torzewski, M., Barlage, S., and Borsukova, H. 2001. Cardiovascular disorders: Atherosclerosis, in Kéri, G. (ed.), Molecular Pathomechanisms and New Tren. in Drug Res. (in press).

  64. Jacobs, M. B. 1994. HMG-CoA reductase inhibitor therapy and peripheral neuropathy. Ann. Intern. Med. 120:970.

    Google Scholar 

  65. Ziajka, P. E. and Wehmeier, T. 1998. Peripheral neuropathy and lipid-lowering therapy. South Med. J. 91:667–668.

    Google Scholar 

  66. Mahley, R. W. 1988. Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 240:622–630.

    Google Scholar 

  67. Popko, B., Goodrum, J. F., Bouldin, T. W., Zhang, S. H., and Maeda, N. 1993. Nerve regeneration occurs in the absence of apolipoprotein E in mice. J. Neurochem. 60:1155–1158.

    Google Scholar 

  68. Goodrum, J. F., Bouldin, T. W., Zhang, S. H., Maeda, N., and Popko, B. 1995. Nerve regeneration and cholesterol utilization occur in the absence of apolipoproteins E and A-I in mice. J. Neurochem. 64:408–416.

    Google Scholar 

  69. Gotthardt, M., Trommsdorff, M., Nevitt, M. F., Shelton, J., Richardson, J. A., Stockinger, W., Nimpf, J., and Herz, J. 2000. Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J. Biol. Chem. 275:25616–25624.

    Google Scholar 

  70. Stockinger, W., Brandes, C., Fasching, D., Hermann, M., Gotthardt, M., Herz, J., Schneider, W. J., and Nimpf, J. 2000. The reelin receptor apoER2 recruits JNK-interacting proteins-1 and-2. J. Biol. Chem. 275:25625–25632.

    Google Scholar 

  71. Van Gool, D., De Strooper, B., Van Leuven, F., Triau, E., and Dom, R. 1993. α2-Macroglobulin expression in neuritic-type plaques in patients with Alzheimer's disease. Neurobiol. Aging 14:233–237.

    Google Scholar 

  72. Hughes, S. R., Khorkova, O., Goyal, S., Knaeblein, J., Heroux, J., Riedel, N. G., and Sahasrabudhe, S. 1998. α2-macroglobulin associates with β-amyloid peptide and prevents fibril formation. Proc. Natl. Acad. Sci. USA 95:3275–3280.

    Google Scholar 

  73. Goldstein, J. L., Ho, Y. K., Basu, S. K., and Brown, M. S. 1979. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc. Natl. Acad. Sci. USA 76:333–337.

    Google Scholar 

  74. De Villiers, W. J. S. and Smart, E. J. 1999. Macrophage scavenger receptors and foam cell formation. J. Leukoc. Biol. 66:740–746.

    Google Scholar 

  75. De Winther, M. P., Van Dijk, K. W., Havekes, L. M., and Hofker, M. H. 2000. Macrophage scavenger receptor class A: A multifunctional receptor in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 20:290–297.

    Google Scholar 

  76. Jessup, W. and Kritharides, L. 2000. Metabolism of oxidized LDL by macrophages. Curr. Opin. Lipidol. 11:473–481.

    Google Scholar 

  77. Bhakdi, S., Dorweiler, B., Kirchmann, R., Torzewski, J., Weise, E., Tmum-Jensen, J., Walev, I., and Wieland, E. 1995. On the pathogenesis of atherosclerosis: Enzymatic transformation of human low density lipoprotein to an atherogenic moiety. J. Exp. Med. 182:1959–1971.

    Google Scholar 

  78. Kovanen, P. T. 1995. Role of mast cells in atherosclerosis. Pages 132–170, in Clinical Immunology, Vol. 62, Human Basophils and Mast Cells, Clinical Aspects, Karger, Basel.

    Google Scholar 

  79. Kapinsky, M., Torzewski, M., Büchler, C., Duong, C. Q., Rothe, G., and Schmitz, G. 2001. Enzymatically degraded LDL preferentially binds to CD14highCD16+ monocytes and induces foam cell formation mediated only in part by the class B scavengerreceptor CD36. Arterioscler. Thromb. Vasc. Biol. (in press)

  80. Khoo, J. C., Miller, E., McLoughlin, P., and Steinberg, D. 1988. Enhanced macrophage uptake of low density lipoprotein after self-aggregation. Arteriosclerosis 8:348–358.

    Google Scholar 

  81. Mamo, J. C., Elsegood, C. L., Gennat, H. C., and Yu, K. 1996. Degradation of chylomicron remnants by macrophages occurs via phagocytosis. Biochemistry 35:10210–10214.

    Google Scholar 

  82. Tabas, I., Lim, S., Xu, X. X., and Maxfield, F. R. 1990. Endocytosed beta-VLDL and LDL are delivered to different intracellular vesicles in mouse peritoneal macrophages. J. Cell Biol. 111:929–940.

    Google Scholar 

  83. Myers, J. N., Tabas, I., Jones, N. L., and Maxfield, F. R. 1993. Beta-very low density lipoprotein is sequestered in surface-connected tubules in mouse peritoneal macrophages. J. Cell Biol. 123:1389–1402.

    Google Scholar 

  84. Kruth, H. S., Skarlatos, S. I., Lilly, K., Chang, J., and Ifrim, I. 1995. Sequestration of acetylated LDL and cholesterol crystals by human monocyte-derived macrophages. J. Cell Biol. 129:133–145.

    Google Scholar 

  85. Stangl, H., Hyatt, M., and Hobbs, H. H. 1999. Transport of lipids from high and low density lipoproteins via scavenger receptor-BI. J. Biol. Chem. 274:32692–32698.

    Google Scholar 

  86. Williams, D. L., Connelly, M. A., Temel, R. E., Swarnakar, S., Phillips, M. C., de la Llera-Moya, M., and Rothblat, G. H. 1999. Scavenger receptor BI and cholesterol trafficking. Curr. Opin. Lipidol. 10:329–339.

    Google Scholar 

  87. Trigatti, B., Rigotti, A., and Krieger, M. 2000. The role of the high-density lipoprotein receptor SR-BI in cholesterol metabolism. Curr. Opin. Lipidol. 11:123–131.

    Google Scholar 

  88. Swarnakar, S., Temel, R. E., Connelly, M. A., Azhar, S., and Williams, D. L. 1999. Scavenger receptor class B, type I, mediates selective uptake of low density lipoprotein cholesteryl ester. J. Biol. Chem. 274:29733–29739.

    Google Scholar 

  89. Acton, S., Rigotti, A., Landschulz, K. T., Xu, S., Hobbs, H. H., and Krieger, M. 1996. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271:518–520.

    Google Scholar 

  90. Gu, X., Trigatti, B., Xu, S., Acton, S., Babitt, J., and Krieger, M. 1998. The efficient cellular uptake of high density lipoprotein lipids via scavenger receptor class B type I requires not only receptor-mediated surface binding but also receptor-specific lipid transfer mediated by its extracellular domain. J. Biol. Chem. 273:26338–26348.

    Google Scholar 

  91. Graf, G. A., Connell, P. M., van der Westhuyzen, D. R., and Smart, E. J. 1999. The class B, type I scavenger receptor promotes the selective uptake of high density cholesteryl ethers into caveolae. J. Biol. Chem. 274:12043–12048.

    Google Scholar 

  92. Rodrigueza, W. V., Thuahnai, S. T., Temel, R. E., Lund-Katz, S., Phillips, M. C., and Williams, D. L. 1999. Mechanism of scavenger receptor class B type I-mediated selective uptake of cholesteryl esters from high density lipoprotein to adrenal cells. J. Biol. Chem. 274:20344–20350.

    Google Scholar 

  93. Fielding, C. J. and Fielding, P. E. 1997. Intracellular cholesterol transport. J. Lipid Res. 38:1503–1521.

    Google Scholar 

  94. Delamatre, J. G., Carter, R. M., and Hornick, C. A. 1993. Evidence that a neutral cholesteryl ester hydrolase is responsible for the extralysosomal hydrolysis of high-density lipoprotein cholesteryl ester in rat hepatoma cells (Fu5AH). J. Cell Physiol. 157:164–168.

    Google Scholar 

  95. Lambert, G., Chase, M. B., Dugi, K., Bensaduon, A., Brewer, H. B. Jr., and Santamarina-Fojo, S. 1999. Hepatic lipase promotes the selective uptake of high density lipoprotein-cholesteryl esters via the scavenger receptor B1. J. Lipid Res. 40:1294–1303.

    Google Scholar 

  96. Collet, X., Tall, A. R., Serajuddin, H., Guendouzi, K., Royer, L., Oliveira, H., Barbaras, R., Jiang, X. C., and Francone, O. L. 1999. Remodeling of HDL by CETP in vivo and by CETP and hepatic lipase in vitro results in enhanced uptake of HDL CE by cells expressing scavenger receptor B-I. J. Lipid Res. 40:1185–1193.

    Google Scholar 

  97. Connelly, M. A., Klein, S. M., Azhar, S., Abumrad, N. A., and Williams, D. L. 1999. Comparison of class B scavenger receptors, CD36 and SR-BI, shows that both receptors mediate HDL-cholesteryl ester selective uptake but SR-BI exhibits a unique enhancement of cholesteryl ester uptake. J. Biol. Chem. 274:41–47.

    Google Scholar 

  98. Aitman T. J., Glazier, A. M., Wallace, C. A., Cooper, L. D., Norsworthy, P. J., Wahid, F. N., Al-Majali, K. M., Trembling, P. M., Mann, C. J., Shoulders, C. C. et al. 1999. Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat. Genet. 21:76–83.

    Google Scholar 

  99. Silverstein, R. L. and Febbraio, M. 2000. CD36 and atherosclerosis. Curr. Opin. Lipidol. 11:483–491.

    Google Scholar 

  100. Wolfbauer, G., Albers, J. J., and Oram, J. F. 1999. Phospholipid transfer protein enhances removal of cellular cholesterol and phospholipids by high-density lipoprotein apolipoproteins. Biochim. Biophys. Acta 1439:65–76.

    Google Scholar 

  101. Frank, P. G. and Marcel, Y. L. 2000. Apolipoprotein A-I: Structure—function relationships. J. Lipid Res. 41:853–872.

    Google Scholar 

  102. Yokoyama, S. 2000. Release of cellular cholesterol: Molecular mechanism for cholesterol homeostasis in cells and in the body. Biochim. Biophys. Acta 1529:231–244.

    Google Scholar 

  103. Segrest, J. P., Li, L., Arantharamaiah, G. M., Harvey, S. C., Liadaki, K. N., and Zannis, V. 2000. Structure and function of apolipoprotein A-I and high-density lipoprotein. Curr. Opin. Lipidol. 11:105–115.

    Google Scholar 

  104. Bodzioch, M., Orsó, E., Klucken, J., Langmann, T., Böttcher, A., Diederich, W., Drobnik, W., Barlage, S., Büchler, C., Porsch-Özcürümez, M., et al. 1999. The gene encoding ATPbinding cassette transporter 1 is mutated in Tangier disease. Nat. Genet. 22:347–351.

    Google Scholar 

  105. Brooks-Wilson, A., Marcil, M., Clee, S. M., Zhang, L-H., Roomp, K., van Dam, M., Yu, L., Brewer, C., Collins, J. A., Molhuizen, H. O. F. et al. 1999. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat. Genet. 22:336–345.

    Google Scholar 

  106. Rust, S., Rosier, M., Funke, H., Real, J., Amoura, Z., Piette, JC., Deleuze, J-F., Brewer, H. B., Duverger, N., Denèfle, P. et al. 1999. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette tarnsporter 1. Nat. Genet. 22:352–355.

    Google Scholar 

  107. Lawn, R. M., Wade, D. P., Garvin, M. R., Wang, X., Schwartz, K., Porter, J. G., Seilhamer, J. J., Vaughan, A. M., and Oram, J. F. 1999. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J. Clin. Invest. 104:R25–R31.

    Google Scholar 

  108. Orsó, E., Broccardo, C., Kaminski, W. E., Böttcher, A., Liebisch, G., Drobnik, W., Götz, A., Chambenoit, O., Diederich, W., Langmann, T. et al. 2000. Transport of lipids from Golgi to plasma membrane is defective in Tangier disease patients and Abc1-deficient mice. Nat. Genet. 24:192–196.

    Google Scholar 

  109. Fielding, P. E., Nagao, K., Hakamata, H., Chimini, G., and Fielding, C. J. 2000. A two-step mechanism for free cholesterol and phospholipid efflux from human vascular cells to apolipoprotein A-I. Biochemistry 39:14113–14120.

    Google Scholar 

  110. Oram, J. F. 2000. Tangier disease and ABCA1. Biochim. Biophys. Acta 1529:321–330.

    Google Scholar 

  111. Schmitz, G. and Langmann, T. 2001. Structure, function and regulation of the ABC1 gene product. Curr. Opin. Lipidol. 12:129–140.

    Google Scholar 

  112. Rosenberg, M. F., Callaghan, R., Ford, R. C., and Higgins, C. F. 1997. Structure of the multidrug resistance P-glycoprotein to 2.5 nm resolution determined by electron microscopy and image analysis. J. Biol. Chem. 272:10685–10694.

    Google Scholar 

  113. Remaley, A. T., Stonik, J. A., Demosky, S. J., Neufeld, E. B., Bocharov, A. V., Vishnyakova, T. G., Eggerman, T. L., Patterson, A. P., Duverger, N. J., Santamarina-Fojo, S. et al. 2001. Apolipoprotein specificity for lipid efflux by the human ABCA1 transporter. Biochem. Biophys. Res. Commun. 280:818–823.

    Google Scholar 

  114. Langmann, T., Klucken, J., Reil, M., Liebisch, G., Luciani, MF., Chimini, G., Kaminski, W. E., and 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.

    Google Scholar 

  115. Michikawa, M., Fan, Q. W., Isobe, I., and Yanagisawa, K. 2000. Apolipoprotein E exhibits isoform-specific promotion of lipid efflux from astrocytes in culture. J. Neurochem. 74:1008–1016.

    Google Scholar 

  116. Ji, Y., Jian, B., Wang, N., Sun, Y., Moya, M. D., Phillips, M. C., Rothblat, G. H., Swaney, J. B., and Tall, A. R. 1997. Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux. J. Biol. Chem. 272:20982–20985.

    Google Scholar 

  117. Jian, B., de la Llera-Moya, M., Ji, Y., Wang, N., Phillips, M. C., Swaney, J. B., Tall, A. R., and Rothblat, G. H. 1998. Scavenger receptor class B type I as a modulator of cellular cholesterol efflux to lipoproteins and phospholipid acceptors. J. Biol. Chem. 273:5599–5606.

    Google Scholar 

  118. Yancey, P. G., Bielicki, J. K., Johnson, W. J., Lund-Katz, S., Palgunachari, M. N., Arantharamaiah, G. M., Segrest, J. P., Phillips, M. C., and Rothblat, G. H. 1995. Efflux of cellular cholesterol and phospholipid to lipid-free apolipoproteins and class A amphipathic peptides. Biochemistry 34:7955–7965.

    Google Scholar 

  119. Mendez, A. J., Oram, J. F., and Bierman, E. L. 1991. Protein kinase C as a mediator of high density lipoprotein receptor-dependent efflux of intracellular cholesterol. J. Biol. Chem. 266:10104–10111.

    Google Scholar 

  120. Choi, S. W., Park, H. Y., Rubeiz, N. G., Sachs, D., and Gilchrest, B. A. 1998. Protein kinase C-alpha levels are inversely associated with growth rate in cultured human dermal fibroblasts. J. Dermatol. Sci. 18:54–63.

    Google Scholar 

  121. Deeg, M. A., Garwer, W. S., Bierman, E. L., and Oram, J. F. 1993. HDL stimulates phosphorylation of 18 and 80 kDa proteins in cholesterol-loaded human skin fibroblasts. (Abstract) Circulation 88:1215.

    Google Scholar 

  122. Deeg, M. A., Bowen, R. F., Oram, J. F., and Bierman, E. L. 1997. High density lipoproteins stimulate mitogen activated protein kinases in human skin fibroblasts. Arterioscler. Thromb. Vasc. Biol. 17:1667–1674.

    Google Scholar 

  123. Walter, M., Reinecke, H., Gerdes, U., Nofer, J-R., Hobbel, G., Seedorf, U., and Assmann, G. 1996. Defective regulation of phosphatidylcholine-specific phospholipases C and D in a kindred with Tangier disease. Evidence for the involvement of phosphatidylcholine breakdown in HDL-mediated cholesterol efflux mechanisms. J. Clin. Invest. 98:2315–2323.

    Google Scholar 

  124. Drobnik, W., Möllers, C., Resink, T., and Schmitz, G. 1995. Activation of phosphatidyl-inositol-specific phospholipase C in response to high density and low density lipoproteins is markedly reduced in cultured fibroblasts from Tangier patients. Arterioscler. Thromb. Vasc. Biol. 15:1369–1377.

    Google Scholar 

  125. Möllers, C., Drobnik, W., Resink, T., and Schmitz, G. 1995. High density and low density lipoprotein-mediated signal transduction in cultured human skin fibroblasts. Cell Signal. 7:695–707.

    Google Scholar 

  126. Mott, S., Yu, L., Marcil, M., Boucher, B., Rondeau, C., and Genest, J. Jr. 2000. Decreased cellular cholesterol efflux is a common cause of familial hypoalphalipoproteinemia: Role of the ABCA1 gene mutations. Atherosclerosis 152:457–468.

    Google Scholar 

  127. Drobnik, W., Liebisch, G., Biederer, C., Trümbach, B., Rogler, G., Müller, P., and Schmitz, G. 1999. Growth and cell cycle abnormalities of fibroblasts from Tangier disease patients. Arterioscler. Thromb. Vasc. Biol. 19:28–38.

    Google Scholar 

  128. Nofer, J-R., Fobker, M., Höbbel, G., Voss, R., Wolinska, I., Tepel, M., Zidek, W., Junker, R., Seedorf, U., von Eckardtstein, A. et al. 2000. Activation of phosphatidylinositol-specific phospholipase C by HDL-associated lysosphingolipid. Involvement in mitogenesis but not in cholesterol efflux. Biochemistry 39:15199–15207.

    Google Scholar 

  129. Schmitz, G., Robenek, H., Lohmann, U., and Assmann, G. 1985. Interaction of high density lipoproteins with cholesteryl ester-laden macrophages: Biochemical and morphological characterization of cell surface receptor binding, endocytosis and resecretion of high density lipoproteins by macrophages. EMBO J. 4:613–622.

    Google Scholar 

  130. Takahashi, Y. and Smith, J. D. 1999. Cholesterol efflux to apolipoprotein Al involves endocytosis and resecretion in a calcium-dependent pathway. Proc. Natl. Acad. Sci. USA 96:11358–11363.

    Google Scholar 

  131. Ho, Y. K., Brown, M. S., and Goldstein, J. L. 1980. Hydrolysis and excretion of cytoplasmic cholesteryl esters by macrophages: stimulation by high density lipoprotein and other agents. J. Lipid Res. 21:391–398.

    Google Scholar 

  132. Robenek, H. and Schmitz, G. 1988. Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. II. Characterization of intracellular morphologic changes. Arteriosclerosis 8:57–67.

    Google Scholar 

  133. Kruth, H. S., Skarlatos, S. I., Gaynor, P. M., and Gamble, W. 1994. Production of cholesterol-enriched nascent high density lipoproteins by human monocyte-derived macrophages is a mechanism that contributes to macrophage cholesterol efflux. J. Biol. Chem. 269:24511–24518.

    Google Scholar 

  134. Albers, J. J., Wolfbauer, G., Cheung, M. C., Day, J. R., Ching, A. F., Lok, S., and Tu, A. Y. 1995. Functional expression of human and mouse plasma phospholipid transfer protein: Effect of recombinant and plasma PLTP on HDL subspecies.

  135. Albers, J. J., Tollefson, J. H., Wolfbauer, G., and Albright, R. E. jr. 1992. Cholesteryl ester transfer protein in human brain. Int. J. Clin. Lab. Res. 21:264–266.

    Google Scholar 

  136. Yamada, T., Kawata, M., Arai, H., Fukasawa, M., Inoue, K., and Sato, T. 1995. Astroglial localization of cholesteryl ester transfer protein in normal and Alzheimer's disease brain tissues. Acta Neuropathol. (Berl.) 90:633–636.

    Google Scholar 

  137. Diczfalusy, U., Lund, E., Lütjohann, D., and Björkhem, I. 1996. Novel pathways for elimination of cholesterol by extrahepatic formation of side-chain oxidized oxysterols. Scand. J. Clin. Lab. Invest. Suppl. 226:9–17.

    Google Scholar 

  138. Björkhem, I., Diczfalusy, U., and Lütjohann, D. 1999. Removal of cholesterol from extrahepatic sources by oxidative mechanisms. Curr. Opin. Lipidol. 10:161–165.

    Google Scholar 

  139. Cohen, J. C. 1999. Contribution of cholesterol 7α-hydroxylase to the regulation of lipoprotein metabolism. Curr. Opin. Lipidol. 10:303–307.

    Google Scholar 

  140. Papassotiropoulos, A., Lütjohann, D., Bagli, M., Locatelli, S., Jessen, F., Rao, M. L., Maier, W., Björkhem, I., von Bergmann, K. et al. 2000. Plasma 24S-hydroxycholesterol: A peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease. NeuroReport 11:1959–1962.

    Google Scholar 

  141. Brown, A. J. and Jessup, W. 1999. Oxysterols and atherosclerosis. Atherosclerosis 142:1–28.

    Google Scholar 

  142. Lagace, T. A., Byers, D. M., Cook, H. W., and Ridgway, N. D. 1997. Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain. Biochem. J. 326:205–213.

    Google Scholar 

  143. Levine, T. P. and Munro, S. 1998. The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes. Curr. Biol. 8:729–739.

    Google Scholar 

  144. Ridgway, N. D., Dawson, P. A., Ho, Y. K., Brown, M. S., and Goldstein, J. L. 1992. Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. J. Cell Biol. 116:307–319.

    Google Scholar 

  145. Dawson, P. A., van der Westhuyzen, D. R., Goldstein, J. L., and Brown, M. S. 1989. Purification of oxysterol binding protein from hamster liver cytosol. J. Biol. Chem. 264:9046–9052.

    Google Scholar 

  146. Ridgway, N. D. and Lagace, T. A. 1995. Brefeldin-A renders Chinese hamster ovary cells insensitive to transcriptional suppression by 25-hydroxycholesterol. J. Biol. Chem. 270:8023–8031.

    Google Scholar 

  147. Fang, M., Kearns, B. G., Gedvilaite, A., Kagiwada, S., Kearns, M., Fung, M. K., and Bankaitis, V. A. 1996. Kes1p shares homology with human oxysterolbinding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis. EMBO J. 15:6447–6459.

    Google Scholar 

  148. Laitinen, S., Olkkonen, V. M., Ehnholm, C., and Ikonen, E. 1999. Family of human oxysterol binding protein (OSBP) homologues. A novel member implicated in brain sterol metabolism. J. Lipid Res. 40:2204–2211.

    Google Scholar 

  149. Olkkonen, V. M. and Ikonen, E. 2000. Genetic defects of intracellular-membrane transport. N. Engl. J. Med. 343:1095–1104.

    Google Scholar 

  150. Pfanner, N., Orci, L., Glick, B. S., Amherdt, M., Arden, S. R., Malhotra, V., and Rothman, J. E. 1989. Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cisternae. Cell 59:95–102.

    Google Scholar 

  151. Ostermann, J., Orci, L., Tani, K., Amherdt, M., Ravazzola, M., Elazar, Z., and Rothman, J. E. 1993. Stepwise assembly of functionally active transport vesicles. Cell 75:1015–1025.

    Google Scholar 

  152. Thiele, C., Hannah, M. J., Fahrenholz, F., and Huttner, W. B. 2000. Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles. Nat. Cell Biol. 2:42–49.

    Google Scholar 

  153. Weigert, R., Siletta, M. G., Spano, S., Turacchio G., Cericola, C., Colanzi, A., Senatore, S., Mancici, R., Polishchuk, E. V., Salmona, M. et al. 1999. CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid. Nature 402:429–433.

    Google Scholar 

  154. Schmidt, A., Wolde, M., Thiele, C., Fest, W., Kratzin, H., Podtelejnikov, A. V., Witke, W., Huttner, W. B., and Söling, H-D. 1999. Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid. Nature 401:133–141.

    Google Scholar 

  155. Huttner, W. B. and Schmidt, A. 2000. Lipids, lipid modification and lipid-protein interaction in membrane budding and fission—insights from the roles of endophilin A1 and synaptophysin in synaptic vesicle endocytosis. Curr. Opin. Neurobiol. 10:543–551.

    Google Scholar 

  156. Kobayashi, T., Beuchat, M. H., Lindsay, M., Frias, S., Palmiter, R. D., Sakuraba, H., Parton, R. G., and Gruenberg, J. 1999. Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport. Nat. Cell Biol. 1:113–118.

    Google Scholar 

  157. Hoekstra, D. and IJzendoom, S. C. D. 2000. Lipid trafficking and sorting: How cholesterol is filling gaps. Curr. Opin. Cell Biol. 12:496–502.

    Google Scholar 

  158. Rogers, D. P. and Bankaitis, V. A. 2000. Phospholipid transfer proteins and physiological functions. Int. Rev. Cytol. 197:35–81.

    Google Scholar 

  159. Li, X., Xie, Z., and Bankaitis, V. A. 2000. Phosphatidylinositol/phosphatidylcholine transfer proteins in yeast. Biochim. Biophys. Acta 1486:55–71.

    Google Scholar 

  160. Alb, J. G. Jr., Kearns, M. A., and Bankaitis, V. A. 1996. Phospholipid metabolism and membrane dynamics. Curr. Opin. Cell Biol. 8:534–541.

    Google Scholar 

  161. Seedorf, U., Ellinghaus, P., and Nofer, J-R. 2000. Sterol carrier protein-2. Biochim. Biophys. Acta 1486:45–54.

    Google Scholar 

  162. Baum, C. L., Reschly, E. J., Gayen, A. K., Groh, M. E., and Schadick, K. 1997. Sterol carrier protein-2 overexpression enhances sterol cycling and inhibits cholesterol ester synthesis and high density lipoprotein cholesterol secretion. J. Biol. Chem. 272:6490–6498.

    Google Scholar 

  163. Seedorf, U., Raabe, M., Ellinghaus, P., Kannenberg, F., Fobker, M., Engel, T., Denis, S., Wouters, F., Wirtz, K. W., Wanders, R. J. et al. 1998. Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev. 12:1189–1201.

    Google Scholar 

  164. Uittenbogaard, A., Ying, Y., and Smart, E. J. 1998. Characterization of a cytosolic heat-shock protein-caveolin chaperone complex. Involvement in cholesterol trafficking. J. Biol. Chem. 273:6525–6532.

    Google Scholar 

  165. Blanchette-Mackie, E. J. and Scow, R. O. 1983. Movement of lipolytic products to mitochondria in brown adipose tissue of young rats: An electron microscope study. J. Lipid Res. 24:229–244.

    Google Scholar 

  166. Scow, R. O. and Blanchette-Mackie, E. J. 1991. Transport of fatty acids and monoacylglycerols in white and brown adipose tissue. Brain Res. Bull. 27:487–491.

    Google Scholar 

  167. Schmitz, G. and Müller, G. 1991. Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. J. Lipid Res. 32:1539–1570.

    Google Scholar 

  168. Amende, L. M., Blanchette-Mackie, E. J., Chernick, S. S., and Scow, R. O. 1985. Effect of pH on visualization of fatty acids as myelin figures in mouse adipose tissue by freeze-fracture electron microscopy. Biochim. Biophys. Acta 837:94–102.

    Google Scholar 

  169. Pietrini, V., Rizzuto, N., Vergani, C., Zen, F., and Milone, F. F. 1985. Neuropathy in Tangier disease: A clinicopathologic study and a review of the literature. Acta Neurol. Scand. 72:495–505.

    Google Scholar 

  170. Gibbels, E., Schaefer, H. E., Runne, U., Schröder, J. M., Haupt, W. F., and Assmann, G. 1985. Severe polyneuropathy in Tangier disease mimicking syringomyelia or leprosy. Clinical, biochemical, electrophysiological, and morphological evaluation, including electron microscopy of nerve, muscle, and skin biopsies. J. Neurol. 232:283–294.

    Google Scholar 

  171. Schmitz, G., Assmann, G., Robenek, H., and Brennhausen, B. 1985. Tangier disease: A disorder of intracellular membrane traffic. Proc. Natl. Acad. Sci. USA 82:6305–6309.

    Google Scholar 

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

    Google Scholar 

  173. Schmitz, G., Fischer, H., Beuck, M., Hoecker, K-P., and Robenek, H. 1990. Dysregulation of lipid metabolism in Tangier-monocyte derived macrophages. Atherosclerosis 10:1010–1019.

    Google Scholar 

  174. Christiansen-Weber, T. A., Voland, J. R., Wu, Y., Ngo, K., Roland, B. L., Nguyen, S., Peterson, P. A., and Fung-Leung, W-P. 2000. Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency. Am. J. Pathol. 157:1017–1029.

    Google Scholar 

  175. Liscum, L. and Klansek, J. J. 1998. Niemann-Pick disease type C. Curr. Opin. Lipidol. 9:131–135.

    Google Scholar 

  176. Neufeld, E. B., Wastney, M., Patel, S., Suresh, S., Cooney, A. M., Dwyer, N. K., Roff, C. F., Ohno, K., Morris, J. A., Carstea, E. D. et al. 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.

    Google Scholar 

  177. Blanchette-Mackie, E. J. 2000. Intracellular cholesterol trafficking: Role of the NPC1 protein. Biochim. Biophys. Acta 1486:171–183.

    Google Scholar 

  178. Ory, D. S. 2000. Niemann-Pick type C: A disorder of cellular cholesterol trafficking. Biochim. Biophys. Acta 1529:331–339.

    Google Scholar 

  179. Meresse, S., Gorvel, J. P., and Chavrier, P. 1995. The rab7 GTPase resides on a vesicular compartment connected to lysosomes. J. Cell Sci. 108:3349–3358.

    Google Scholar 

  180. Lombardi, D., Soldati, T., Riederer, M. A., Goda, Y., Zerial, M., and Pfeiffer, S. R. 1993. Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J. 12:677–682.

    Google Scholar 

  181. Garver, W. S., Erickson, R. P., Wilson, J. M., Colton, T. L., Hossain, G. S., Kozloski, M. A., and Heidenreich, R. A. 1997. Altered expression of caveolin-1 and increased cholesterol in detergent insoluble membrane fractions from liver in mice with Niemann-Pick disease type C. Biochim. Biophys. Acta 1361:272–280.

    Google Scholar 

  182. Garver, W. S., Heidenreich, R. A., Erickson, R. P., Thomas, M. A., and Wilson, J. M. 2000. Localization of the murine Niemann-Pick C1 protein to two distinct intracellular compartments. J. Lipid Res. 41:673–687.

    Google Scholar 

  183. Osborne, T. F. and Rosenfeld, J. M. 1998. Related membrane domains in proteins of sterol sensing and cell signaling provide a glimpse of treasures still buried within the dynamic realm of intracellular metabolic regulation. Curr. Opin. Lipidol. 9:137–140.

    Google Scholar 

  184. Carstea, E. D., Morris, J. A., Coleman, K. G., Loftus, S. K., Zhang, D., Cummings, C., Gu, J., Rosenfeld, M. A., Pavan, W. J., Krizman, D. B. et al. 1997. Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis. Science 277:228–231.

    Google Scholar 

  185. Ioannou, Y. A. 2000. The structure and function of the Niemann-Pick C1 protein. Mol. Genet. Metab. 71:175–181.

    Google Scholar 

  186. Morris, J. A., Zhang, D., Coleman, K. G., Nagle, J., Pentchev, P. G., and Carstea, E. D. 1999. The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene. Biochem. Biophys. Res. Commun. 261:493–498.

    Google Scholar 

  187. Patel, S. C., Suresh, S., Kumar, U., Hu, C. Y., Cooney, A., Blanchette-Mackie, E. J., Neufeld, E. B., Patel, R. C., Brady, R. O., Patel, Y. C. et al. 1999. Localization of Niemann-Pick C1 protein in astrocytes: Implications for neuronal degeneration in Niemann-Pick type C disease. Proc. Natl. Acad. Sci. USA 96:1657–1662.

    Google Scholar 

  188. Liu, Y., Wu, Y. P., Wada, R., Neufeld, E. B., Mullin, K. A., Howard, A. C., Pentchev, P. G., Vanier, M. T., Suzuki, K., and Proia, R. L. 2000. Alleviation of neuronal ganglioside storage does not improve the clinical course of the Niemann-Pick C disease mouse. Hum. Mol. Genet. 9:1087–1092.

    Google Scholar 

  189. Naureckiene, S., Sleat, D. E., Lackland, H., Fensom, A., Vanier, M. T., Wattiaux, R., Jadot, M., and Lobel, P. 2000. Identification of HE1 as the second gene of Niemann-Pick C disease. Science 290:2298–2301.

    Google Scholar 

  190. St. George-Hyslop, P. H., Farrer, L. A., and Goedert, M. 2001. Alzheimer disease and the frontotemporal dementias: Diseases with cerebral deposition of fibrillar proteins. Pages 5875–5899, in Scriver, C. R., Beaudet, A. L., Sly, W. S., Valie, D., Childs, B., Kinzler, K. W., and Vogelstein, B. (eds.) The Metabolic & Molecular Bases of Inherited Disease, 8th edition, McGraw-Hill, New York.

    Google Scholar 

  191. Nunan, J. and Small, D. H. 2000. Regulation of APP cleavage by α-, α-and α-secretases. FEBS Lett. 483:6–10.

    Google Scholar 

  192. Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., Song, Y. Q., Rogaeva, E., Chen, F., Kawarai, T. et al. 2000. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing. Nature 407:48–54.

    Google Scholar 

  193. Schenk, D. 2000. A partner for presenilin. Nature 407:34–35.

    Google Scholar 

  194. Lambert, J-C., Mann, D., Goumidi, L., Harris, J., Amouyel, P., Iwatsubo, T., Lendon, C., and Chartier-Harlin, M-C. 2001. Effect of the APOE promoter polymorphisms on cerebral amyloid peptide deposition in Alzheimer's disease. Lancet 357:608–609.

    Google Scholar 

  195. Curtiss, L. K. and Boisvert, W. A. 2000. Apolipoprotein E and atherosclerosis. Curr. Opin. Lipidol. 11:243–251.

    Google Scholar 

  196. Saunders, A. M. 2000. Apolipoprotein E and Alzheimer disease: An update on genetic and functional analyses. J. Neuropathol. Exp. Neurol. 59:751–758.

    Google Scholar 

  197. Zerangue, N., Malan, M. J., Fried, S. R., Dazin, P. F., Jan, Y. N., Jan, L. Y., and Schwappach, B. 2001. Analysis of endoplasmic reticulum trafficking signals by combinatorial screening in mammalian cells. Proc. Natl. Acad. Sci. USA 98:2431–2436.

    Google Scholar 

  198. Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altsteil, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J. et al. 1997. Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. Nat. Genet. 17:263–264.

    Google Scholar 

  199. Chen, M. and Fernandez, H. L. 2001. Where do Alzheimer's plaques and tangles come from? Aging-induced protein degradation inefficiency.

  200. Ilveskoski, E., Jarvinen, O., Sisto, T., Karhunen, P. J., Laippala, P., and Lehtimaki, T. 2000. Apolipoprotein E polymorphism and atherosclerosis: Association of the ε4 allele with defects in the internal elastic lamina. Atherosclerosis 153:155–160.

    Google Scholar 

  201. Stöhr, J., Schindler, G., Rothe, G., and Schmitz, G. 1998. Enhanced upregulation of the Fc gamma receptor Illa (CD16a) during in vitro differentiation of ApoE4/4 monocytes. Arterioscler. Thromb. Vasc. Biol. 18:1424–1432.

    Google Scholar 

  202. Rothe, G., Gabriel, H., Kovács, E., Klucken, J., Stöhr, J., Kindermann, W., and Schmitz, G. 1996. Peripheral blood mononuclear phagocyte subpopulations as cellular markers in hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 16:1437–1447.

    Google Scholar 

  203. Rothe, G., Herr, A. S., Stöhr, J., Abletshauser, C., Weidinger, G., and Schmitz, G. 1999. A more mature phenotype of blood mononuclear phagocytes is induced by fluvastatin treatment in hypercholesterolemic patients with coronary heart disease. Atherosclerosis 144:251–261.

    Google Scholar 

  204. Fingerle, G., Pforte, A., Passlick, B., Blumenstein, M., Strobel, M., and Ziegler-Heitbrock, H. W. 1993. The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients. Blood 82:3170–3176.

    Google Scholar 

  205. Vanham, G., Edmonds, K., Qing, L., Hom, D., Toossi, Z., Jones, B., Daley, C. L., Huebner, B., Kestens, L., Gigase, P. et al. 1996. Generalized immune activation in pulmonary tuberculosis: Co-activation with HIV infection. Clin. Exp. Immunol. 103:30–34.

    Google Scholar 

  206. Schmid, I., Baldwin, G. C., Jacobs, E. L., Isacescu, V., Neagos, N., Giorgi, J. V., and Glaspy, J. A. 1995. Alterations in phenotype and cell-surface antigen expression levels of human monocytes: Differential response to in vivo administration of rhM-CSF or rhGM-CSF. Cytometry 22:103–110.

    Google Scholar 

  207. Saleh, M. N., Goldman, S. J., LoBuglio, A. F., Beall, A. C., Sabio, H., McCord, M. C., Minasian, L., Alpaugh, R. K., Weiner, L. M., and Munn, D. H. 1995. CD16+ monocytes in patients with cancer: Spontaneous elevation and pharmacologic induction by recombinant human macrophage colonystimulating factor. Blood 85:2910–2917.

    Google Scholar 

  208. Scuteri, A., Bos, A. J. G., Zonderman, A. B., Brant, L. J., Lakatta, E. G., and Fleg, J. L. 2001. Is the apoE4 allele an independent predictor of coronary events? Am. J. Med. 110:28–32.

    Google Scholar 

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Schmitz, G., Orsó, E. Intracellular Cholesterol and Phospholipid Trafficking: Comparable Mechanisms in Macrophages and Neuronal Cells. Neurochem Res 26, 1045–1068 (2001). https://doi.org/10.1023/A:1012357106398

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