Sterol-binding proteins and endosomal cholesterol transport

Abstract

Endosomal compartments sort and deliver exogenous lipoprotein-derived cholesterol to the endoplasmic reticulum for regulating cellular cholesterol homeostasis. A large number of studies have focused on the removal of endosomal cholesterol, since its accumulation leads to devastating human diseases. Recent studies suggest that cytoplasmic sterol-binding proteins may be involved in endosomal cholesterol transport. In particular, endosome/lysosome-localized or-associated cholesterol-binding proteins may serve as key mediators of cholesterol removal in a non-vesicular manner. Further characterization of these cholesterol-binding proteins will shed light on the molecular mechanisms that regulate endosomal cholesterol sorting.

Key words： NPC1; NPC2; OSBP/ORP; StAR protein; endosomal cholesterol transport

Acknowledgements

This work is jointly supported by research grants from the Ara Parseghian Medical Research Foundation and the National Health and Medical Research Council of Australia (#510271). X. D. is a recipient of an Early Career in Research Award in the Faculty of Science, University of New South Wales. H. Y. is an inaugural Future Fellow of the Australian Research Council.

References

1 Alpy F, Stoeckel M E, Dierich A, Escola J M, Wendling C, Chenard M P, Vanier M T, Gruenberg J, Tomasetto C, Rio M C (2001). The steroidogenic acute regulatory protein homolog MLN64, a late endosomal cholesterol-binding protein. J Biol Chem, 276(6): 4261-4269

PMID

2 Beh C T, Cool L, Phillips J, Rine J (2001). Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics, 157(3): 1117-1140

PMID

3 Bishop N, Woodman P (2000). ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking. Mol Biol Cell, 11(1): 227-239

PMID

4 Brown M S, Goldstein J L (1986). A receptor-mediated pathway for cholesterol homeostasis. Science, 232(4746): 34-47

PMID

5 Brown M S, Goldstein J L (2009). Cholesterol feedback: from Schoenheimer’s bottle to Scap’s MELADL. J Lipid Res, 50(Suppl): S15-S27

PMID

6 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, Nagle J, Polymeropoulos M H, Sturley S L, Ioannou Y A, Higgins M E, Comly M, Cooney A, Brown A, Kaneski C R, Blanchette-Mackie E J, Dwyer N K, Neufeld E B, Chang T Y, Liscum L, Strauss J F 3rd, Ohno K, Zeigler M, Carmi R, Sokol J, Markie D, O’Neill R R, van Diggelen O P, Elleder M, Patterson M C, Brady R O, Vanier M T, Pentchev P G, Tagle D A (1997). Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science, 277(5323): 228-231

PMID

7 Chang T Y, Chang C C, Ohgami N, Yamauchi Y (2006). Cholesterol sensing, trafficking, and esterification. Annu Rev Cell Dev Biol, 22(1): 129-157

PMID

8 Charman M, Kennedy B E, Osborne N, Karten B (2010). MLN64 mediates egress of cholesterol from endosomes to mitochondria in the absence of functional Niemann-Pick Type C1 protein. J Lipid Res, 51(5): 1023-1034

PMID

9 Davies J P, Ioannou Y A (2000). Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating protein. J Biol Chem, 275(32): 24367-24374

PMID

10 Du X, Kumar J, Ferguson C, Schulz T A, Ong Y S, Hong W, Prinz W A, Parton R G, Brown A J, Yang H (2011). A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. J Cell Biol, 192(1): 121-135

PMID

11 Goldstein J L, DeBose-Boyd R A, Brown M S (2006). Protein sensors for membrane sterols. Cell, 124(1): 35-46

PMID

12 Harrison K D, Miao R Q, Fernandez-Hernándo C, Suárez Y, Dávalos A, Sessa W C (2009). Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular cholesterol trafficking. Cell Metab, 10(3): 208-218

PMID

13 Holtta-Vuori M, Ikonen E (2006). Endosomal cholesterol traffic: vesicular and non-vesicular mechanisms meet. Biochem Soc Trans, 34(Pt 3): 392-394

PMID

14 Ikonen E (2008). Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol, 9(2): 125-138

PMID

15 Im Y J, Raychaudhuri S, Prinz W A, Hurley J H (2005). Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature, 437(7055): 154-158

PMID

16 Infante R E, Abi-Mosleh L, Radhakrishnan A, Dale J D, Brown M S, Goldstein J L (2008a). Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein. J Biol Chem, 283(2): 1052-1063

PMID

17 Infante R E, Radhakrishnan A, Abi-Mosleh L, Kinch L N, Wang M L, Grishin N V, Goldstein J L, Brown M S (2008b). Purified NPC1 protein: II. Localization of sterol binding to a 240-amino acid soluble luminal loop. J Biol Chem, 283(2): 1064-1075

PMID

18 Infante R E, Wang M L, Radhakrishnan A, Kwon H J, Brown M S, Goldstein J L (2008c). NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes. Proc Natl Acad Sci USA, 105(40): 15287-15292

PMID

19 Kwon H J, Abi-Mosleh L, Wang M L, Deisenhofer J, Goldstein J L, Brown M S, Infante R E (2009). Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. Cell, 137(7): 1213-1224

PMID

20 Lavigne P, Najmanivich R, Lehoux J G (2010). Mammalian StAR-related lipid transfer (START) domains with specificity for cholesterol: structural conservation and mechanism of reversible binding. Subcell Biochem, 51: 425-437

PMID

21 Lehto M, Laitinen S, Chinetti G, Johansson M, Ehnholm C, Staels B, Ikonen E, Olkkonen V M (2001). The OSBP-related protein family in humans. J Lipid Res, 42(8): 1203-1213

PMID

22 Lev S (2010). Non-vesicular lipid transport by lipid-transfer proteins and beyond. Nat Rev Mol Cell Biol, 11(10): 739-750

PMID

23 Lingwood D, Simons K (2010). Lipid rafts as a membrane-organizing principle. Science, 327(5961): 46-50

PMID

24 Liu B, Turley S D, Burns D K, Miller A M, Repa J J, Dietschy J M (2009). Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1^-/- mouse. Proc Natl Acad Sci USA, 106(7): 2377-2382

PMID

25 Loewen C J, Roy A, Levine T P (2003). A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. EMBO J, 22(9): 2025-2035

PMID

26 Maxfield F R, van Meer G (2010). Cholesterol, the central lipid of mammalian cells. Curr Opin Cell Biol, 22(4): 422-429

PMID

27 Mesmin B, Maxfield F R (2009). Intracellular sterol dynamics. Biochim Biophys Acta, 1791(7): 636-645

PMID

28 Naureckiene S, Sleat D E, Lackland H, Fensom A, Vanier M T, Wattiaux R, Jadot M, Lobel P (2000). Identification of HE1 as the second gene of Niemann-Pick C disease. Science, 290(5500): 2298-2301

PMID

29 Ngo M H, Colbourne T R, Ridgway N D (2010). Functional implications of sterol transport by the oxysterol-binding protein gene family. Biochem J, 429(1): 13-24

PMID

30 Ohgami N, Ko D C, Thomas M, Scott M P, Chang C C, Chang T Y (2004). Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain. Proc Natl Acad Sci USA, 101(34): 12473-12478

PMID

31 Ohsaki Y, Sugimoto Y, Suzuki M, Hosokawa H, Yoshimori T, Davies J P, Ioannou Y A, Vanier M T, Ohno K, Ninomiya H (2006). Cholesterol depletion facilitates ubiquitylation of NPC1 and its association with SKD1/Vps4. J Cell Sci, 119(Pt 13): 2643-2653

PMID

32 Okamura N, Kiuchi S, Tamba M, Kashima T, Hiramoto S, Baba T, Dacheux F, Dacheux J L, Sugita Y, Jin Y Z (1999). A porcine homolog of the major secretory protein of human epididymis, HE1, specifically binds cholesterol. Biochim Biophys Acta, 1438(3): 377-387

PMID

33 Rigotti A, Cohen D E, Zanlungo S (2010). STARTing to understand MLN64 function in cholesterol transport. J Lipid Res, 51(8): 2015-2017

PMID

34 Rosenbaum A I, Zhang G, Warren J D, Maxfield F R (2010). Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells. Proc Natl Acad Sci USA, 107(12): 5477-5482

PMID

35 Schulz T A, Choi M G, Raychaudhuri S, Mears J A, Ghirlando R, Hinshaw J E, Prinz W A (2009). Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues. J Cell Biol, 187(6): 889-903

PMID

36 Sleat D E, Wiseman J A, El-Banna M, Price S M, Verot L, Shen M M, Tint G S, Vanier M T, Walkley S U, Lobel P (2004). Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci USA, 101(16): 5886-5891

PMID

37 Soccio R E, Breslow J L (2003). StAR-related lipid transfer (START) proteins: mediators of intracellular lipid metabolism. J Biol Chem, 278(25): 22183-22186

PMID

38 Soccio R E, Breslow J L (2004). Intracellular cholesterol transport. Arterioscler Thromb Vasc Biol, 24(7): 1150-1160

PMID

39 Subramanian K, Balch W E (2008). NPC1/NPC2 function as a tag team duo to mobilize cholesterol. Proc Natl Acad Sci USA, 105(40): 15223-15224

PMID

40 Suchanek M, Hynynen R, Wohlfahrt G, Lehto M, Johansson M, Saarinen H, Radzikowska A, Thiele C, Olkkonen V M (2007). The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket. Biochem J, 405(3): 473-480

PMID

41 Taylor F R, Saucier S E, Shown E P, Parish E J, Kandutsch A A (1984). Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme A reductase. J Biol Chem, 259(20): 12382-12387

PMID

42 Wang M L, Motamed M, Infante R E, Abi-Mosleh L, Kwon H J, Brown M S, Goldstein J L (2010). Identification of surface residues on Niemann-Pick C2 essential for hydrophobic handoff of cholesterol to NPC1 in lysosomes. Cell Metab, 12(2): 166-173

PMID

43 Wang P, Zhang Y, Li H, Chieu H K, Munn A L, Yang H (2005a). AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism. EMBO J, 24(17): 2989-2999

PMID

44 Wang P Y, Weng J, Anderson R G (2005b). OSBP is a cholesterol-regulated scaffolding protein in control of ERK1/2 activation. Science, 307(5714): 1472-1476

PMID

45 Willenborg M, Schmidt C K, Braun P, Landgrebe J, von Figura K, Saftig P, Eskelinen E L (2005). Mannose 6-phosphate receptors, Niemann-Pick C2 protein, and lysosomal cholesterol accumulation. J Lipid Res, 46(12): 2559-2569

PMID

46 Wyles J P, McMaster C R, Ridgway N D (2002). Vesicle-associated membrane protein-associated protein-A (VAP-A) interacts with the oxysterol-binding protein to modify export from the endoplasmic reticulum. J Biol Chem, 277(33): 29908-29918

PMID

47 Xu S, Benoff B, Liou H L, Lobel P, Stock A M (2007). Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease. J Biol Chem, 282(32): 23525-23531

PMID

48 Yan D, Mäyränpää M I, Wong J, Perttilä J, Lehto M, Jauhiainen M, Kovanen P T, Ehnholm C, Brown A J, Olkkonen V M (2008). OSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol efflux from macrophages. J Biol Chem, 283(1): 332-340

PMID

49 Yan D, Olkkonen V M (2008). Characteristics of oxysterol binding proteins. Int Rev Cytol, 265: 253-285

PMID

50 Yang H (2006). Nonvesicular sterol transport: two protein families and a sterol sensor? Trends Cell Biol, 16(9): 427-432

PMID