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Cellular Lipid Metabolism pp 157–190Cite as

Intracellular Cholesterol Transport

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Abstract

Cholesterol is the single most abundant lipid species in mammalian cells. More than 2×109 years of evolution designed this molecule to perfectly fit into phospholipid bilayers regulating the fluidity, permeability and bending stiffness of biological membranes. Cholesterol also serves as a precursor of steroid hormones, bile acids and oxysterols, and its cellular synthesis is regulated by a complex machinery. While the molecular mechanisms underlying cholesterol synthesis are known in great detail, knowledge is rather sparse about the inter-compartment transport of cholesterol, including trafficking modes and kinetics, as well as control of endomembrane cholesterol content. This chapter provides an overview of our recent understanding of intracellular transport of cholesterol. It is aimed to create a link between the well characterized biophysical properties of cholesterol in model membranes and its behavior in living cells.

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References

  • Ahmed SN, Brown DA, London E (1997) On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes: physiological concentrations of cholesterol and sphingolipid induce formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes. Biochemistry 36:10944–10953

    Article  PubMed  CAS  Google Scholar 

  • Alpy F, Tomasetto C (2005) Give lipids a START: the StAR-related lipid transfer (START) domain in mammals. J Cell Sci 118:2791–2801

    Article  PubMed  CAS  Google Scholar 

  • Babalola JO, Wendeler M, Breiden B, Arenz C, Schwarzmann G, Locatelli-Hoops S, Sandhoff K (2007) Development of an assay for the intermembrane transfer of cholesterol by Niemann-Pick C2 protein. Biol Chem 388:617–626

    Article  PubMed  CAS  Google Scholar 

  • Bar LK, Barenholz Y, Thompson TE (1986) Fraction of cholesterol undergoing spontaneous exchange between small unilamellar phosphatidylcholine vesicles. Biochemistry 25:6701–6705

    Article  PubMed  CAS  Google Scholar 

  • Bar LK, Barenholz Y, Thompson TE (1987) Dependence on phospholipid composition of the fraction of cholesterol undergoing spontaneous exchange between small unilamellar vesicles. Biochemistry 26:5460–5465

    Article  PubMed  CAS  Google Scholar 

  • Baumann NA, Sullivan DP, Ohvo-Rekila H, Simonot C, Pottekat A, Klaassen Z, Beh CT, Menon AK (2005) Transport of newly synthesized sterol to the sterol-enriched plasma membrane occurs via nonvesicular equilibration. Biochemistry 44:5816–5826

    Article  PubMed  CAS  Google Scholar 

  • Becker T, Volchuk A, Rothman JE (2005) Differential use of endoplasmic reticulum membrane for phagocytosis in J774 macrophages. Proc Natl Acad Sci USA 102:4022–4026

    Article  PubMed  CAS  Google Scholar 

  • Behnke O, Tranum-Jensen J, van Deurs B (1984a) Filipin as a cholesterol probe. I. Morphology of filipin-cholesterol interaction in lipid model systems. Eur J Cell Biol 35:189–199

    CAS  Google Scholar 

  • Behnke O, Tranum-Jensen J, van Deurs B (1984b) Filipin as a cholesterol probe. II. Filipin-cholesterol interaction in red blood cell membranes. Eur J Cell Biol 35:200–215

    PubMed  CAS  Google Scholar 

  • Bonifacino JS, Lippincott-Schwartz J (2003) Coat proteins: shaping membrane transport. Nat Rev Mol Cell Biol 4:409–414

    Article  PubMed  CAS  Google Scholar 

  • Boucrot E, Saffarian S, Massol R, Kirchhausen T, Ehrlich M (2006) Role of lipids and actin in the formation of clathrin-coated pits. Exp Cell Res 312:4036–4048

    Article  PubMed  CAS  Google Scholar 

  • Bridgman PC, Nakajima Y (1983) Distribution of filipin-sterol complexes on cultured muscle cells: cell-substratum contact areas associated with acetylcholine clusters. J Cell Biol 96:363–372

    Article  PubMed  CAS  Google Scholar 

  • Buton X, Mamdouh Z, Ghosh RN, Du H, Kuriakose G, Beatini N, Grabowski GA, Maxfield FR, Tabas I (1999) Unique cellular events occurring during the initial interaction of macrophages with matrix-retained or methylated aggregated low density lipoprotein (LDL). Prolonged cell-surface contact during which LDL-cholesteryl ester hydrolysis exceeds LDL protein degradation. J Biol Chem 274:32112–32121

    Article  PubMed  CAS  Google Scholar 

  • Cantor RS (1999) Lipid composition and the lateral pressure profile in bilayers. Biophys J 76:2625–2639

    Article  PubMed  CAS  Google Scholar 

  • Chatterjee S, Smith ER, Hanada K, Stevens VL, Mayor S (2001) GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment. EMBO J 20:1583–1592

    Article  PubMed  CAS  Google Scholar 

  • Chattopadhyay A, Jafurulla M, Kalipatnapu S, Pucadyil TJ, Harikumar KG (2005) Role of cholesterol in ligand binding and G-protein coupling of serotonin(1A) receptors solubilized from bovine hippocampus. Biochem Biophys Res Commun 327:1036–1041

    Article  PubMed  CAS  Google Scholar 

  • Cheruku SR, Xu Z, Dutia R, Lobel P, Storch J (2006) Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model membranes supports a role in lysosomal cholesterol transport. J Biol Chem 281:31594–31604

    Article  PubMed  CAS  Google Scholar 

  • Choudhury A, Sharma DK, Marks DL, Pagano RE (2004) Elevated endosomal cholesterol levels in Niemann-Pick cells inhibit rab4 and perturb membrane recycling. Mol Biol Cell 15:4500–4511

    Article  PubMed  CAS  Google Scholar 

  • Corvera S, DiBonaventura C, Shpetner HS (2000) Cell confluence-dependent remodeling of endothelial membranes mediated by cholesterol. J Biol Chem 275:31414–31421

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Cruz JC, Chang TY (2000) Fate of endogenously synthesized cholesterol in Niemann-Pick type C1 cells. J Biol Chem 275:41309–41316

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • DeGrella RF, Simoni RD (1982) Intracellular transport of cholesterol to the plasma membrane. J Biol Chem 257:14256–14262

    PubMed  CAS  Google Scholar 

  • Dragsten PR, Blumenthal R, Handler JS (1981) Membrane asymmetry in epithelia: is the tight junction a barrier to diffusion in the plasma membrane. Nature 294:718–722

    Article  PubMed  CAS  Google Scholar 

  • Du X, Pham YH, Brown AJ (2004) Effects of 25-hydroxycholesterol on cholesterol esterification and sterol regulatory element-binding protein processing are dissociable: implications for cholesterol movement to the regulatory pool in the endoplasmic reticulum. J Biol Chem 279:47010–47016

    Article  PubMed  CAS  Google Scholar 

  • Edidin M (2003) Lipids on the frontier: a century of cell-membrane bilayers. Nat Cell Biol 4:414–418

    Article  CAS  Google Scholar 

  • Eskelinen EL, Schmidt CK, Neu S, Willenborg M, Fuertes G, Salvador N, Tanaka Y, Lüllmann-Rauch R, Hartmann D, Heeren J, von Figura K, Knecht E, Saftig P (2004) Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell 15:3132–3145

    Article  PubMed  CAS  Google Scholar 

  • 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 (2003a) The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5:781–792

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Friedland N, Liou H-L, Lobel P, Stock AM (2003) Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc Natl Acad Sci USA 100:2512–2517

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara T, Ritchie K, Murakoshi H, Jacobson K, Kusumi A (2002) Phospholipids undergo hop diffusion in compartmentalized cell membrane. J Cell Biol 157:1071–1081

    Article  PubMed  CAS  Google Scholar 

  • Futerman AH, van Meer G (2004) The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol 5:554–565

    Article  PubMed  CAS  Google Scholar 

  • Ganguly S, Pucadyil TJ, Chattopadhyay A (2008) Actin cytoskeleton-dependent dynamics of the human serotonin(1A) receptor correlates with receptor signaling. Biophys J 95:451–463

    Article  PubMed  CAS  Google Scholar 

  • Ganley IG, Pfeffer SR (2006) Cholesterol accumulation sequesters Rab9 and disrupts late endosome function in NPC1-deficient cells. J Biol Chem 281:17890–17899

    Article  PubMed  CAS  Google Scholar 

  • Garver WS, Krishnan K, Gallagos JR, Michikawa M, Francis GA, Heidenreich RA (2002) Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J Lipid Res 43:579–589

    PubMed  CAS  Google Scholar 

  • Garvik O, Benediktson P, Ipsen JH, Simonsen AC, Wüstner D (2009) The fluorescent cholesterol analog dehydroergosterol induces liquid-ordered domains in model membranes. Chem Phys Lipids (in press)

    Google Scholar 

  • Gliss C, Randel O, Casalta H, Sackmann E, Zorn R, Bayerl T (1999) Anisotropic motion of cholesterol in oriented DPPC bilayers studied by quasielastic neutron scattering: the liquid-ordered phase. Biophys J 77:331–340

    Article  PubMed  CAS  Google Scholar 

  • Goldstein JL, Brown MS (1974) Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem 249

    Google Scholar 

  • Goldstein JL, DeBose-Boyd RA, Brown MS (2006) Protein sensors for membrane sterols. Cell 124:35–46

    Article  PubMed  CAS  Google Scholar 

  • Goodwin JS, Drake KR, Remmert CL, Kenworthy AK (2005) Ras diffusion is sensitive to plasma membrane viscosity. Biophys J 89:1398–1410

    Article  PubMed  CAS  Google Scholar 

  • Graf GA, Li WP, Gerard RD, Gelissen I, White A, Cohen JC, Hobbs HH (2002) Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface. J Clin Invest 110:659–669

    PubMed  CAS  Google Scholar 

  • Grimmer S, van Deurs B, Sandvig K (2002) Membrane ruffling and macropinocytosis in A431 cells require cholesterol. J Cell Sci 115:2953–2962

    PubMed  CAS  Google Scholar 

  • Grimmer S, Ying M, Wälchli S, van Deurs B, Sandvig K (2005) Golgi vesiculation induced by cholesterol occurs by a dynamin- and cPLA2-dependent mechanism. Traffic 6:144–156

    Article  PubMed  CAS  Google Scholar 

  • Haberland ME, Reynolds JA (1973) Self-association of cholesterol in aqueous solution. Proc Natl Acad Sci USA 70:2313–2318

    Article  PubMed  CAS  Google Scholar 

  • Hamilton JA (2003) Fast flip-flop of cholesterol and fatty acids in membranes: implications for membrane transport proteins. Curr Opin Lipidol 14:263–271

    Article  PubMed  CAS  Google Scholar 

  • Hao M, Mukherjee S, Sun Y, Maxfield FR (2004) Effects of cholesterol depletion and increased lipid unsaturation on the properties of endocytic membranes. J Biol Chem 279:14171–14178

    Article  PubMed  CAS  Google Scholar 

  • Hao M, Lin SX, Karylowski OJ, Wüstner D, McGraw TE, Maxfield FR (2002) Vesicular and non-vesicular sterol transport in living cells. The endocytic recycling compartment is a major sterol storage organelle. J Biol Chem 277:609–617

    Article  PubMed  CAS  Google Scholar 

  • Harikumar KG, Puri V, Singh RD, Hanada K, Pagano RE, Miller LJ (2005) Differential effects of modification of membrane cholesterol and sphingolipids on the conformation, function, trafficking of the G protein-coupled cholecystokinin receptor. J Biol Chem 280:2176–2185

    Article  PubMed  CAS  Google Scholar 

  • Hartwig Petersen N, Færgeman NJ, Yu L, Wüstner D (2008) Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells. J Lipid Res 49:2023–2037

    Article  CAS  Google Scholar 

  • Heerklotz H (2002) Triton promotes domain formation in lipid raft mixtures. Biophys J 83:2693–2701

    Article  PubMed  CAS  Google Scholar 

  • Heino S, Lusa S, Somerharju P, Ehnholm C, Olkkonen VM, Ikonen E (2000) Dissecting the role of the golgi complex and lipid rafts in biosynthetic transport of cholesterol to the cell surface. Proc Natl Acad Sci USA 97:8375–8380

    Article  PubMed  CAS  Google Scholar 

  • Hell SW (2007) Far-field optical nanoscopy. Science 316:1153–1158

    Article  PubMed  CAS  Google Scholar 

  • Henriksen J, Rowat AC, Ipsen JH (2004) Vesicle fluctuation analysis of the effects of sterols on membrane bending rigidity. Eur Biophys J 33:732–741

    Article  PubMed  CAS  Google Scholar 

  • Henriksen J, Rowat AC, Brief E, Hsueh YW, Thewalt JL, Zuckermann MJ, Ipsen JH (2006) Universal behavior of membranes with sterols. Biophys J 90:1639–1649

    Article  PubMed  CAS  Google Scholar 

  • Hess ST, Gould TJ, Gudheti MV, Maas SA, Mills KD, Zimmerberg J (2007) Dynamic clustered distribution of hemagglutinin resolved at 40 nm in living cell membranes discriminates between raft theories. Proc Natl Acad Sci USA 104:17370–17375

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Hill WG, Zeidel ML (2000) Reconstituting the barrier properties of a water-tight epithelial membrane by design of leaflet-specific liposomes. J Biol Chem 275:30176–30185

    Article  PubMed  CAS  Google Scholar 

  • Hofsass, C, E. Lindahl, O. Edholm (2003) Molecular dynamics simulations of phospholipid bilayers with cholesterol. Biophys. J. 84:2192–2206.- 6.

    Article  PubMed  CAS  Google Scholar 

  • Hölttä-Vuori M, Tanhuanpää K, Möbius W, Somerharju P, Ikonen E (2002) Modulation of cellular cholesterol transport and homeostasis by Rab11. Mol Biol Cell 13:3107–3122

    Article  PubMed  CAS  Google Scholar 

  • Hölttä-Vuori M, Alpy F, Tanhuanpaa K, Jokitalo E, Mutka AL, Ikonen E (2005) MLN64 is involved in actin-mediated dynamics of late endocytic organelles. Mol Biol Cell 16:3873–3886

    Article  PubMed  CAS  Google Scholar 

  • Hornick CA, Hui DY, DeLamatre JG (1997) A role for retrosomes in intracellular cholesterol transport from endosomes to the plasma membrane. Am J Physiol 273:C1075–C1081

    PubMed  CAS  Google Scholar 

  • Huang J, Feigenson GW (1999) A microscopic interaction model of maximum solubility of cholesterol in lipid bilayers. Biophys J 76:2142–2157

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Buboltz JT, Feigenson GW (1999) Maximum solubility of cholesterol in phosphatidylcholine and phosphatidylethanolamine bilayers. Biochim Biophys Acta 1417:89–100

    Article  PubMed  CAS  Google Scholar 

  • Infante RE, Radhakrishnan A, Abi-Mosleh L, Kinch LN, Wang ML, Grishin NV, Goldstein JL, Brown MS (2008) Purified NPC1 protein: II. Localization of sterol binding to a 240-amino-acid soluble luminal loop. J Biol Chem 283:1064–1075

    Article  PubMed  CAS  Google Scholar 

  • Infante RE, Abi-Mosleh L, Radhakrishnan A, Dale JD, Brown MS, Goldstein JL (2008) Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino-acid membrane protein. J Biol Chem 283:1052–1063

    Article  PubMed  CAS  Google Scholar 

  • Infante RE, Wang ML, Radhakrishnan A, Kwon HJ, Brown MS, Goldstein JL (2008) NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes. Proc Natl Acad Sci USA 105:15287–15292

    Article  PubMed  CAS  Google Scholar 

  • Ipsen JH, Karlstrom G, Mouritsen OG, Wennerstrom H, Zuckermann MJ (1987) Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim Biophys Acta 905:162–172

    Article  PubMed  CAS  Google Scholar 

  • John K, Kubelt J, Müller P, Wüstner D, Herrmann A (2002) Rapid transbilayer movement of the fluorescent sterol dehydroergosterol in lipid membranes. Biophys J 83:1525–1534

    Article  PubMed  CAS  Google Scholar 

  • Jost M, Simpson F, Kavran JM, Lemmon MA, Schmid SL (1998) Phosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation. Curr Biol 8:1399–1402

    Article  PubMed  CAS  Google Scholar 

  • Kaplan MR, et al (1985) Transport of cholesterol from the endoplasmic reticulum to the plasma membrane. J Cell Biol 101:446–453

    Article  PubMed  CAS  Google Scholar 

  • Karnovsky MJ, Kleinfeld AM, Hoover RL, Klausner RD (1982) The concept of lipid domains in membranes. J Cell Biol 94:1–6

    Article  PubMed  CAS  Google Scholar 

  • Kaufmann AM, Krise JP (2008) Niemann-Pick C1 functions in regulating lysosomal amine content. J Biol Chem 283:24584–24593

    Article  PubMed  CAS  Google Scholar 

  • Kellner-Weibel G, Yancey PG, Jerome WG, Walser T, Mason RP, Phillips MC, Rothblat GH (1999) Crystallization of free cholesterol in model macrophage foam cells. Arterioscler Thromb Vasc Biol 19:1891–1898

    Article  PubMed  CAS  Google Scholar 

  • Kenworthy AK (2008) Have we become overly reliant on lipid rafts? Talking Point on the involvement of lipid rafts in T-cell activation. EMBO Rep 9:531–535

    Article  PubMed  CAS  Google Scholar 

  • Kenworthy AK, Nichols BJ, Remmert CL, Hendrix GM, Kumar M, Zimmerberg J, Lippincott-Schwartz J (2004) Dynamics of putative raft–associated proteins at the cell surface. J Cell Biol 165:735–746

    Article  PubMed  CAS  Google Scholar 

  • Khan N, Shen J, Chang TY, Chang CC, Fung PC, Grinberg O, Demidenko E, Swartz H (2003) Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal and mutant CHO cells defective in cholesterol metabolism. Biochemistry 42:23–29

    Article  PubMed  CAS  Google Scholar 

  • Khelef N, Soe TT, Quehenberger O, Beatini N, Tabas I, Maxfield FR (2000) Enrichment of acyl coenzyme A:cholesterol O-acyltransferase near trans-Golgi network and endocytic recycling compartment. Arterioscler Thromb Vasc Biol 20:1769–1776

    Article  PubMed  CAS  Google Scholar 

  • Khelef N, Buton X, Beatini N, Wang H, Meiner V, Chang TY, Farese RVJ, Maxfield FR, Tabas I (1998) Immunolocalization of acyl-coenzyme A:cholesterol O-acyltransferase in macrophages. J Biol Chem 273:11218–11224

    Article  PubMed  CAS  Google Scholar 

  • Ko DC, Gordon MD, Jin JY, Scott MP (2001) Dynamic movements of organelles containing Niemann-Pick C1 protein: NPC1 involvement in late endocytic events. Mol Biol Cell 12:601–614

    PubMed  CAS  Google Scholar 

  • Kobayashi T, Beuchat MH, Lindsay M, Frias S, Palmiter RD, Sakuraba H, Parton RG, Gruenberg J (1999) Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport. Nat Cell Biol 1:113–118

    Article  PubMed  CAS  Google Scholar 

  • Koppel DE, Sheetz MP, Schindler M (1981) Matrix control of protein diffusion in biological membranes. Proc Natl Acad Sci USA 78:6981–6985

    Article  Google Scholar 

  • Kristiana I, Yang H, Brown AJ (2008) Different kinetics of cholesterol delivery to components of the cholesterol homeostatic machinery: implications for cholesterol trafficking to the endoplasmic reticulum. Biochim Biophys Acta. 1781:724–730

    Google Scholar 

  • Krylov AV, Pohl P, Zeidel ML, Hill WG (2001) Water permeability of asymmetric planar lipid bilayers: leaflets of different composition offer independent and additive resistance to permeation. J Gen Physiol 118:333–339

    Article  PubMed  CAS  Google Scholar 

  • Kwik J, Boyle S, Fooksman D, Margolis L, Sheetz MP, Edidin M (2003) Membrane cholesterol, lateral mobility, the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin. Proc Natl Acad Sci USA 100:13964–13969

    Article  PubMed  CAS  Google Scholar 

  • Ladinsky MS, Mastronarde DN, McIntosh JR, Howell KE, Staehelin LA (1999) Golgi structure in three dimensions: functional insights from the normal rat kidney cell. J Cell Biol 144:1135–1149

    Article  PubMed  CAS  Google Scholar 

  • Lang T, Bruns D, Wenzel D, Riedel D, Holroyd P, Thiele C, Jahn R (2001) SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis. EMBO J 20:2202–2213

    Article  PubMed  CAS  Google Scholar 

  • Lange Y, Matthies HJ (1984) Transfer of cholesterol from its site of synthesis to the plasma membrane. J Biol Chem 259:14624–14630

    PubMed  CAS  Google Scholar 

  • Lange Y, Steck TL (2008) Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol. Prog Lipid Res 47:319–332

    Article  PubMed  CAS  Google Scholar 

  • Lange Y, Echevarria F, Steck TL (1991) Movement of Zymosterol, a precursor of cholesterol, among three membranes in human fibroblasts. J Biol Chem 266:21439–21443

    PubMed  CAS  Google Scholar 

  • Lange Y, Ye J, Rigney M, Steck TL (1999) Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol. J Lipid Res 40:2264–2270

    PubMed  CAS  Google Scholar 

  • Lange Y, Swaisgood MH, Ramos BV, Steck TL (1989) Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts. J Biol Chem 264:3786–3793

    PubMed  CAS  Google Scholar 

  • Lebrand C, Corti M, Goodson H, Cosson P, Cavalli V, Mayran N, Fauré J, Gruenberg J (2002) Late endosome motility depends on lipids via the small GTPase Rab7. EMBO J 21:1289–1300

    Article  PubMed  CAS  Google Scholar 

  • Leventis R, Silvius JR (2001) Use of cyclodextrins to monitor transbilayer movement and differential lipid affinities of cholesterol. Biophys J 81:2257–2267

    Article  PubMed  CAS  Google Scholar 

  • Levine T, Loewen C (2006) Inter-organelle membrane contact sites: through a glass, darkly. Curr Opin Cell Biol 18:371–378

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Prinz WA (2004) ATP-binding cassette (ABC) transporters mediate nonvesicular, raft-modulated sterol movement from the plasma membrane to the endoplasmic reticulum. J Biol Chem 279:45226–45234

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Ge M, Ciani L, Kuriakose G, Westover EJ, Dura M, Covey DF, Freed JH, Maxfield FR, Lytton J, Tabas I (2004) Enrichment of endoplasmic reticulum with cholesterol inhibits sarcoplasmic-endoplasmic reticulum calcium ATPase-2b activity in parallel with increased order of membrane lipids: implications for depletion of endoplasmic reticulum calcium stores and apoptosis in cholesterol-loaded macrophages. J Biol Chem 279:37030–37039

    Article  PubMed  CAS  Google Scholar 

  • Lindahl E, Edholm O (2000) Spatial and energetic-entropic decomposition of surface tension in lipid bilayers from molecular dynamics simulations. J Chem Phys 113:3882–3893

    Article  CAS  Google Scholar 

  • Linder MD, Uronen RL, Holtta-Vuori M, van der Sluijs P, Peranen J, Ikonen E (2006) Rab8-dependent recycling promotes endosomal cholesterol removal in normal and sphingolipidosis cells. Mol Biol Cell 18:47–56

    Article  PubMed  CAS  Google Scholar 

  • Liou HL, Dixit SS, Xu S, Tint GS, Stock AM, Lobel P (2006) NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols. J Biol Chem 281:36710–36723

    Article  PubMed  CAS  Google Scholar 

  • Lippincott-Schwartz J, Yuan L, Tipper C, Amherdt M, Orci L, Klausner RD (1991) Brefeldin A’s effects on endosomes, lysosomes, the TGN suggest a general mechanism for regulating organelle structure and membrane traffic. Cell 67:601–616

    Article  PubMed  CAS  Google Scholar 

  • Liscum L, Munn NJ (1999) Intracellular cholesterol transport. Biochim Biophys Acta 1438:19–37

    PubMed  CAS  Google Scholar 

  • Liscum L, Sturley SL (2004) Intracellular trafficking of Niemann-Pick C proteins 1 and 2: obligate components of subcellular lipid transport. Biochim Biophys Acta 1685:22–27

    PubMed  CAS  Google Scholar 

  • Lloyd-Evans E, Morgan AJ, He X, Smith DA, Elliot-Smith E, Sillence DJ, Churchill GC, Schuchman EH, Galione A, Platt FM (2008) Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med. 14:1247–1255

    Google Scholar 

  • Loomis CR, Shipley GG, Small DM (1979) The phase behavior of hydrated cholesterol. J Lipid Res 20:525–535

    PubMed  CAS  Google Scholar 

  • Luzio JP, Bright NA, Pryor PR (2007) The role of calcium and other ions in sorting and delivery in the late endocytic pathway. Biochem Soc Trans 35:1088–1091

    Article  PubMed  CAS  Google Scholar 

  • Mallard F, Tang BL, Galli T, Tenza D, Saint-Pol A, Yue X, Antony C, Hong W, Goud B, Johannes L (2002) Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. J Cell Biol 156:653–664

    Article  PubMed  CAS  Google Scholar 

  • Maxfield FR (2002) Plasma membrane microdomains. Curr Opin Cell Biol 14:483–487

    Article  PubMed  CAS  Google Scholar 

  • Maxfield FR, Menon AK (2006) Intracellular sterol transport and distribution. Curr Opin Cell Biol 18:379–385

    Article  PubMed  CAS  Google Scholar 

  • Maxfield FR, Wüstner D (2002) Intracellular cholesterol transport. J Clin Invest 110:891–898

    PubMed  CAS  Google Scholar 

  • Maxfield FR, Tabas I (2005) Role of cholesterol and lipid organization in disease. Nature 438:612–621

    Article  PubMed  CAS  Google Scholar 

  • Maxfield FR, McGraw TE (2004) Endocytic recycling. Nat Rev Mol Cell Biol 5:121–132

    Article  PubMed  CAS  Google Scholar 

  • Mayor S, Maxfield FR (1995) Insolubility and redistribution of GPI-anchored proteins at the cell surface after detergent treatment. Mol Biol Cell 6:929–944

    PubMed  CAS  Google Scholar 

  • Mayor S, Pagano RE (2007) Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol 8:603–612

    Article  PubMed  CAS  Google Scholar 

  • Mayor S, Sabharanjak S, Maxfield FR (1998) Cholesterol-dependent retention of GPI-anchored proteins in endosomes. EMBO J 17:4626–4638

    Article  PubMed  CAS  Google Scholar 

  • McConnell HM, Radhakrishnan A (2003) Condensed complexes of cholesterol and phospholipids. Biochim et Biophys Acta 1610:159–173

    Article  CAS  Google Scholar 

  • Miaczynska M, Zerial M (2002) Mosaic organization of the endocytic pathway. Exp Cell Res 272:8–14

    Article  PubMed  CAS  Google Scholar 

  • Millard EE, Gale SE, Dudley N, Zhang J, Schaffer JE, Ory DS (2005) The sterol-sensing domain of the Niemann-Pick C1 (NPC1) protein regulates trafficking of low density lipoprotein cholesterol. J Biol Chem 280:28581–28590

    Article  PubMed  CAS  Google Scholar 

  • Möbius W, van Donselaar E, Ohno-Iwashita Y, Shimada Y, Heijnen HF, Slot JW, Geuze HJ (2003) Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway. Traffic 64:222–231

    Article  Google Scholar 

  • Montesano R (1979) Inhomogeneous distribution of filipin-sterol complexes in smooth muscle cell plasma membrane. Nature 280:328–329

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee S, Maxfield FR (2004) Lipid and cholesterol trafficking in NPC. Biochim Biophys Acta 1685:28–37

    PubMed  CAS  Google Scholar 

  • Mukherjee S, Maxfield FR (2004) Membrane domains. Annu Rev Cell Dev Biol 20:839–866

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee S, Ghosh RN, Maxfield FR (1997) Endocytosis. Physiol Rev 77:759–803

    PubMed  CAS  Google Scholar 

  • Munro S (2003) Lipid rafts: elusive or illusive. Cell 115:377–388

    Article  PubMed  CAS  Google Scholar 

  • Murcia M, Faraldo-Gomez JD, Maxfield FR, Roux B (2006) Modeling the structure of the START domains of MLN64 and StAR proteins in complex with cholesterol. J Lipid Res 47:2614–2630

    Article  PubMed  CAS  Google Scholar 

  • Murray JW, Wolkoff AW (2003) Roles of the cytoskeleton and motor proteins in endocytic sorting. Adv Drug Deliv Rev 55:1385–1403

    Article  PubMed  CAS  Google Scholar 

  • Nagao T, Qin C, Grosheva I, Maxfield FR, Pierini LM (2007) Elevated cholesterol levels in the plasma membranes of macrophages inhibit migration by disrupting RhoA regulation. Arterioscler Thromb Vasc Biol 27:1596–1602

    Article  PubMed  CAS  Google Scholar 

  • Nagle JF, Tristram-Nagle S (2000) Structure of lipid bilayers. Biochim Biophys Acta 1469:159–195

    PubMed  CAS  Google Scholar 

  • Narita K, Choudhury A, Dobrenis K, Sharma DK, Holicky EL, Marks DL, Walkley SU, Pagano RE (2005) Protein transduction of Rab9 in Niemann-Pick C cells reduces cholesterol storage. FASEB J 19:1558–1560

    PubMed  CAS  Google Scholar 

  • 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 

  • Needham D, McIntosh TJ, Evans E (1988) Thermomechanical and transition properties of dimyristoylphosphatidylcholine/cholesterol bilayers. Biochemistry 27:4668–4673

    Article  PubMed  CAS  Google Scholar 

  • Neufeld EB, Cooney AM, Pitha J, Dawidowicz EA, Dwyer NK, Pentchev PG, Blanchette-Mackie EJ (1996) Intracellular trafficking of cholesterol monitored with a cyclodextrin. J Biol Chem 271:21604–21613

    Article  PubMed  CAS  Google Scholar 

  • Neufeld EB, Wastney M, Patel S, Suresh S, Cooney AM, Dwyer NK, Roff CF, Ohno K, Morris JA, Carstea ED, Incardona JP, Strauss JFR, 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 

  • Nilsson I, Ohvo-Rekila H, Slotte JP, Johnson AE, von Heijne G (2001) Inhibition of protein translocation across the endoplasmic reticulum membrane by sterols. J Biol Chem 276:41748–41754

    Article  PubMed  CAS  Google Scholar 

  • Niu S-L, Litman BJ (2002) Determination of membrane cholesterol partition coefficient using a lipid vesicle-cyclodextrin binary system: effect of phospholipid acyl chain unsaturation and headgroup composition. Biophys J 83:3408–3415

    Article  PubMed  CAS  Google Scholar 

  • Ohvo-Rekila H, Ramstedt B, Leppimaki P, Slotte JP (2002) Cholesterol interactions with phospholipids in membranes. Prog Lipid Res 41:66–97

    Article  PubMed  CAS  Google Scholar 

  • op den Kamp JAF (1979) Lipid asymmetry in membranes. Biochemistry 48:47–71

    Article  CAS  Google Scholar 

  • Passeggio J, Liscum L (2005) Flux of fatty acids through NPC1 lysosomes. J Biol Chem 280:10333–10339

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer SR (2007) Unsolved mysteries in membrane traffic. Annu Rev Biochem 76:629–645

    Article  PubMed  CAS  Google Scholar 

  • Pierini LM, Eddy RJ, Fuortes M, Seveau S, Casulo C, Maxfield FR (2003) Membrane lipid organization is critical for human neutrophil polarization. J Biol Chem 278:10831–10841

    Article  PubMed  CAS  Google Scholar 

  • Pipalia NH, Hao M, Mukherjee S, Maxfield FR (2006) Sterol, protein and lipid trafficking in Chinese hamster ovary cells with Niemann-Pick type C1 defect. Traffic 8:130–141

    Article  PubMed  CAS  Google Scholar 

  • Piper RC, Luzio JP (2004) CUPpling calcium to lysosomal biogenesis. Trends Cell Biol 14:471–473

    Article  PubMed  CAS  Google Scholar 

  • Pomorski T, Holthuis JC, Herrmann A, van Meer G (2004) Tracking down lipid flippases and their biological functions. J Cell Sci 117:805–813

    Article  PubMed  CAS  Google Scholar 

  • Pralle A, Keller P, Florin EL, Simons K, Horber JK (2000) Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J Cell Biol 148:997–1008

    Article  PubMed  CAS  Google Scholar 

  • Prattes S, Horl G, Hammer A, Blaschitz A, Graier WF, Sattler W, Zechner R, Steyrer E (2000) Intracellular distribution and mobilization of unesterified cholesterol in adipocytes: triglyceride droplets are surrounded by cholesterol-rich ER-like surface layer structures. J Cell Sci 113:2977–2989

    PubMed  CAS  Google Scholar 

  • Puri V, Watanabe R, Dominguez M, Sun X, Wheatley CL, Marks DL, Pagano RE (1999) Cholesterol modulates membrane traffic along the endocytic pathway in sphingolipid-storage diseases. Nat Cell Biol 1:386–388

    Article  PubMed  CAS  Google Scholar 

  • Puri V, Watanabe R, Singh RD, Dominguez M, Brown JC, Wheatley CL, Marks DL, Pagano RE (2001) Clathrin-dependent and -independent internalization of plasma membrane sphingolipids initiates two Golgi targeting pathways. J Cell Biol 154:535–547

    Article  PubMed  CAS  Google Scholar 

  • Qin C, Nagao T, Grosheva I, Maxfield FR, Pierini LM (2006) Elevated plasma membrane cholesterol content alters macrophage signaling and function. Arterioscler Thromb Vasc Biol 26:372–378

    Article  PubMed  CAS  Google Scholar 

  • Radhakrishnan A, McConnell HM (2000) Chemical activity of cholesterol in membranes. Biochemistry 39:8119–8124

    Article  PubMed  CAS  Google Scholar 

  • Ridsdale A, Denis M, Gougeon PY, Ngsee JK, Presley JF, Zha X (2006) Cholesterol is required for efficient endoplasmic reticulum-to-Golgi transport of secretory membrane proteins. Mol Biol Cell 17:1593–1605

    Article  PubMed  CAS  Google Scholar 

  • Rink J, Ghigo E, Kalaidzidis Y, Zerial M (2005) Rab conversion as a mechanism of progression from early to late endosomes. Cell 122:735–749

    Article  CAS  Google Scholar 

  • Robinet P, Fradagrada A, Monier MN, Marchetti M, Cogny A, Moatti N, Paul JL, Vedie B, Lamaze C (2006) Dynamin is involved in endolysosomal cholesterol delivery to the endoplasmic reticulum: role in cholesterol homeostasis. Traffic 7:811–823

    Article  PubMed  CAS  Google Scholar 

  • Robins SJ, Fasulo JM (1999) Delineation of a novel hepatic route for the selective transfer of unesterified sterols from high-density lipoproteins to bile: studies using the perfused rat liver. Hepatology 29:1541–1548

    Article  PubMed  CAS  Google Scholar 

  • Róg T, Stimson LM, Pasenkiewicz-Gierula M, Vattulainen I, Karttunen M (2008) Replacing the cholesterol hydroxyl group with the ketone group facilitates sterol flip-flop and promotes membrane fluidity. J Phys Chem B 112:1946–1952

    Article  PubMed  CAS  Google Scholar 

  • Runz H, Miura K, Weiss M, Pepperkok R (2006) Sterols regulate ER-export dynamics of secretory cargo protein ts-O45-G. EMBO J 25:2953–2965

    Article  PubMed  CAS  Google Scholar 

  • Rusiñol AE, Cui Z, Chen MH, Vance JE (1994) A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J Biol Chem 269:27494–27502

    PubMed  Google Scholar 

  • Sako Y, Kusumi A (1995) Barriers for lateral diffusion of transferrin receptor in the plasma membrane as characterized by receptor dragging by laser tweezers: fence versus tether. J Cell Biol 129:1559–1574

    Article  PubMed  CAS  Google Scholar 

  • Sandvig K, Torgersen ML, Raa HA, van Deurs B (2008) Clathrin-independent endocytosis: from nonexisting to an extreme degree of complexity. Histochem. Cell Biol 129:267–276

    Article  PubMed  CAS  Google Scholar 

  • Scheidt HA, Müller P, Herrmann A, Huster D (2003) The potential of fluorescent and spin-labeled steroid analogs to mimic natural cholesterol. J Biol Chem 278:45563–45569

    Article  PubMed  CAS  Google Scholar 

  • Sharma DK, Brown JC, Choudhury A, Peterson TE, Holicky E, Marks DL, Simari R, Parton RG, Pagano RE (2004) Selective stimulation of caveolar endocytosis by glycosphingolipids and cholesterol. Mol Biol Cell 15:3114–3122

    Article  PubMed  CAS  Google Scholar 

  • Sheetz MP (2001) Cell control by membrane cytoskeleton adhesion. Nat Rev Mol Cell Biol 2:392–396

    Article  PubMed  CAS  Google Scholar 

  • Shiratori Y, Okwu AK, Tabas I (1994) Free cholesterol loading of macrophages stimulates phosphatidylcholine biosynthesis and up-regulation of CTP: phosphocholine cytidylyltransferase. J Biol Chem 269:11337–11348

    PubMed  CAS  Google Scholar 

  • Shvartsman DE, Gutman O, Tietz A, Henis YI (2006) Cyclodextrins but not compactin inhibit the lateral diffusion of membrane proteins independent of cholesterol. Traffic 7:917–926

    Article  PubMed  CAS  Google Scholar 

  • Sieber JJ, Willig KI, Kutzner C, Gerding-Reimers C, Harke B, Donnert G, Rammner B, Eggeling C, Hell SW, Grubmüller H, Lang T (2007) Anatomy and dynamics of a supramolecular membrane protein cluster. Science 317:1072–1076

    Article  PubMed  CAS  Google Scholar 

  • Sieber JJ, Willig KI, Heintzmann R, Hell SW, Lang T (2006) The SNARE motif is essential for the formation of syntaxin clusters in the plasma membrane. Biophys J 90:2843–2851

    Article  PubMed  CAS  Google Scholar 

  • Silvius JR, del Giudice D, Lafleur M (1996) Cholesterol at different bilayer concentrations can promote or antagonize lateral segregation of phospholipids of differing acyl chain length. Biochemistry 35:15198–15208

    Article  PubMed  CAS  Google Scholar 

  • Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    Article  PubMed  CAS  Google Scholar 

  • Simons K, van Meer G (1988) Lipid sorting in epithelial cells. Biochemistry 27:6197–6202

    Article  PubMed  CAS  Google Scholar 

  • 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 USA 101:5886–5891

    Article  PubMed  CAS  Google Scholar 

  • Small et al (1974) Physical-chemical basis of lipid deposition in atherosclerosis. Science 185:222–229

    Article  PubMed  CAS  Google Scholar 

  • Snapp EL, Hegde RS, Francolini M, Lombardo F, Colombo S, Pedrazzini E, Borgese N, Lippincott-Schwartz J (2003) Formation of stacked ER cisternae by low affinity protein interactions. J Cell Biol 163:257–269

    Article  PubMed  CAS  Google Scholar 

  • Somerharju P, Virtanen JA, Cheng KH (1999) Lateral organisation of membrane lipids. The superlattice view. Biochim Biophys Acta 1440:32–48

    PubMed  CAS  Google Scholar 

  • Steck TL, Kezdy FJ, Lange Y (1988) An activation-collision mechanism for cholesterol transfer between membranes. J Biol Chem 263:13023–13031

    PubMed  CAS  Google Scholar 

  • Steck TL, Ye J, Lange Y (2002) Probing red cell membrane cholesterol movement with cyclodextrin. Biophys J 83:2118–2125

    Article  PubMed  CAS  Google Scholar 

  • Subczynski WK, Kusumi A (2003) Dynamics of raft molecules in the cell and artificial membranes: approaches by pulse EPR spin labeling and single molecule optical microscopy. Biochim Biophys Acta 1610:231–243

    Article  PubMed  CAS  Google Scholar 

  • Subczynski WK, Hyde JS, Kusumi A (1989) Oxygen permeability of phosphatidylcholine-cholesterol membranes. Proc Natl Acad Sci USA 86:4474–4478

    Article  PubMed  CAS  Google Scholar 

  • Sun M, Northup N, Marga F, Huber T, Byfield FJ, Levitan I, Forgacs G (2007) The effect of cellular cholesterol on membrane-cytoskeleton adhesion. J Cell Sci 120:2223–2231

    Article  PubMed  CAS  Google Scholar 

  • Tabas I (2000) Cholesterol and phospholipid metabolism in macrophages. Biochim Biophys Acta 1529:164–174

    PubMed  CAS  Google Scholar 

  • Tabas I, Rosoff WJ, Boykow GC (1988) Acyl coenzyme A:cholesterol acyl transferase in macrophages utilizes a cellular pool of cholesterol oxidase-accessible cholesterol as substrate. J Biol Chem 263:1266–1272

    PubMed  CAS  Google Scholar 

  • Takahashi M, Murate M, Fukuda M, Sato SB, Ohta A, Kobayashi T (2007) Cholesterol controls lipid endocytosis through Rab11. Mol Biol Cell 18:2667–2677

    Article  PubMed  CAS  Google Scholar 

  • Tall AR, Costet P, Wang N (2002) Regulation and mechanisms of macrophage cholesterol efflux. J Clin Invest 110:899–904

    PubMed  CAS  Google Scholar 

  • Tangirala RK, Jerome WG, Jones NL, Small DM, Johnson WJ, Glick JM, Mahlberg FH, Rothblat GH (1994) Formation of cholesterol monohydrate crystals in macrophage-derived foam cells. J Lipid Res 35:93–104

    PubMed  CAS  Google Scholar 

  • Tomishige MY, Sako Y, Kusumi A (1998) Regulation mechanism of the lateral diffusion of band 3 in erythrocyte membranes by membrane cytoskeleton. J Cell Biol 142:989–1000

    Article  PubMed  CAS  Google Scholar 

  • Underwood KW, Jacobs NL, Howley A, Liscum L (1998) Evidence for a cholesterol transport pathway from lysosomes to endoplasmic reticulum that is independent of the plasma membrane. J Biol Chem 273:4266–4274

    Article  PubMed  CAS  Google Scholar 

  • Urano Y, Watanabe H, Murphy SR, Shibuya Y, Geng Y, Peden AA, Chang CC, Chang TY (2008) Transport of LDL-derived cholesterol from the NPC1 compartment to the ER involves the trans-Golgi network and the SNARE protein complex. Proc Natl Acad Sci USA 105:16513–16518

    Article  PubMed  CAS  Google Scholar 

  • van Dam EM, Ten Broeke T, Jansen K, Spijkers P, Stoorvogel W (2002) Endocytosed transferrin receptors recycle via distinct dynamin and phosphatidylinositol 3-kinase-dependent pathways. J Biol Chem 277:48876–48883

    Article  PubMed  CAS  Google Scholar 

  • van der Goot FG, Gruenberg J (2006) Intra-endosomal membrane traffic. Trends Cell Biol 16:514–521

    Article  PubMed  CAS  Google Scholar 

  • Vist MR, Davis JH (1990) Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: 2H nuclear magnetic resonance and differential scanning calorimetry. Biochemistry 29:451–464

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Castoreno AB, Stockinger W, Nohturfft A (2005) Modulation of endosomal cholesteryl ester metabolism by membrane cholesterol. J Biol Chem 280:11876–11886

    Article  PubMed  CAS  Google Scholar 

  • Warnock DE, Roberts C, Lutz MS, Blackburn WA, Young WWJ, Baenziger JU (1993) Determination of plasma membrane lipid mass and composition in cultured Chinese hamster ovary cells using high gradient magnetic affinity chromatography. J Biol Chem 268:10145–10153

    PubMed  CAS  Google Scholar 

  • Wattenberg BW, Silbert DF (1983) Sterol partitioning among intracellular membranes. Testing a model for cellular sterol distribution. J Biol Chem 258:2284–2289

    PubMed  CAS  Google Scholar 

  • Wilcke M, Johannes L, Galli T, Mayau V, Goud B, Salamero J (2000) Rab11 regulates the compartmentalization of early endosomes required for efficient transport from early endosomes to the trans-Golgi network. J Cell Biol 151:1207–1220

    Article  PubMed  CAS  Google Scholar 

  • Willenborg M, Schmidt CK, Braun P, Landgrebe J, von Figura K, Saftig P, Eskelinen EL (2005) Mannose 6-phosphate receptors, Niemann-Pick C2 protein, lysosomal cholesterol accumulation. J Lipid Res 46:2559–2569

    Article  PubMed  CAS  Google Scholar 

  • Wojtanik KM, Liscum L (2003) The transport of low density lipoprotein-derived cholesterol to the plasma membrane is defective in NPC1 cells. J Biol Chem 278:14850–14856

    Article  PubMed  CAS  Google Scholar 

  • Wüstner D (2005) Improved visualization and quantitative analysis of fluorescent membrane sterol in polarized hepatic cells. J Microsc 220:47–64

    Article  PubMed  Google Scholar 

  • Wüstner D (2007) Fluorescent sterols as tools in membrane biophysics and cell biology. Chem Phys Lipids 146:1–25

    Article  PubMed  CAS  Google Scholar 

  • Wüstner D (2007) Plasma membrane sterol distribution resembles the surface topography of living cells. Mol Biol Cell 18:211–228

    Article  PubMed  CAS  Google Scholar 

  • Wüstner D (2008) Free-cholesterol loading does not trigger phase separation of the fluorescent sterol dehydroergosterol in the plasma membrane of macrophages. Chem Phys Lipids 154:129–136

    Article  PubMed  CAS  Google Scholar 

  • Wüstner D, Herrmann A, Hao M, Maxfield FR (2002) Rapid nonvesicular transport of sterol between the plasma membrane domains of polarized hepatic cells. J Biol Chem 277:30325–30336

    Article  PubMed  Google Scholar 

  • Wüstner D, Færgeman NJ (2008) Spatiotemporal analysis of endocytosis and membrane distribution of fluorescent sterols in living cells. Histochem Cell Biol 130:891–908

    Article  PubMed  CAS  Google Scholar 

  • Wüstner D, Mondal M, Huang A, Maxfield FR (2004) Different transport routes for high density lipoprotein and its associated free sterol in polarized hepatic cells. J Lipid Res 45:427–437

    Article  PubMed  CAS  Google Scholar 

  • Wüstner D, Mondal M, Tabas I, Maxfield FR (2005) Direct observation of rapid internalization and intracellular transport of sterol by macrophage foam cells. Traffic 6:396–412

    Article  PubMed  CAS  Google Scholar 

  • Wüstner D, Landt Larsen A, Sage D, Bagatolli LA, Færgeman NJ, Brewer JR (2009) One- and three-photon fluorescence microscopy for imaging of dehydroergosterol in living cells and organisms. (Submitted for publication)

    Google Scholar 

  • Xu XX, Tabas I (1991) Lipoproteins activate acyl-coenzyme A:cholesterol acyltransferase in macrophages only after cellular cholesterol pools are expanded to a critical threshold level. J Biol Chem 266:17040–17048

    PubMed  CAS  Google Scholar 

  • Xu Z, Farver W, Kodukula S, Storch J (2008) Regulation of sterol transport between membranes and NPC2. Biochemistry 47:11134–11143

    Article  PubMed  CAS  Google Scholar 

  • Yeagle PL (1985) Cholesterol and the cell membrane. Biochim Biophys Acta 822:267–287

    PubMed  CAS  Google Scholar 

  • Ying M, Grimmer S, Iversen TG, van Deurs B, Sandvig K (2003) Cholesterol loading induces a block in the exit of VSVG from the TGN. Traffic 4:772–784

    Article  PubMed  CAS  Google Scholar 

  • Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, Hobbs HH (2002) Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 110:671–680

    PubMed  CAS  Google Scholar 

  • Zhang M, Dwyer NK, Love DC, Cooney A, Comly M, Neufeld E, Pentchev PG, Blanchette-Mackie EJ, Hanover JA (2001) Cessation of rapid late endosomal tubulovesicular trafficking in Niemann–Pick type C1 disease. Proc Natl Acad Sci USA 98:4466–4471

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, McIntosh AL, Xu H, Wu D, Gruninger T, Atshaves B, Liu JC, Schroeder F (2005) Structural analysis of sterol distributions in the plasma membrane of living cells. Biochemistry 44:2864–2884

    Article  PubMed  CAS  Google Scholar 

  • Zoncu R, Perera RM, Sebastian R, Nakatsu F, Chen H, Balla T, Ayala G, Toomre D, De Camilli PV (2007) Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proc Natl Acad Sci USA 104:3793–3798

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

I acknowledge funding by grants from the Danish Heart Association Hjerteforeningen, the Diabetes Foundation Diabetesforeningen and the Danish Research Agency Forskningsstyrelsen, Forskningsrådet for Natur og Univers. Dr. Adam Cohen Simonsen from the Department of Physics and Chemistry, Center for Membrane Physics (MEMPHYS) at the University of Southern Denmark is acknowledged for providing the AFM images shown in Fig. 6.2.

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    Daniel Wüstner

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    Wüstner, D. (2009). Intracellular Cholesterol Transport. In: Ehnholm, C. (eds) Cellular Lipid Metabolism. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00300-4_6

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