Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption

Journal of Lipid Research

Volumn 50, Issue 8, 2009, Pages 1653-1662

  Wang, Jiang ^a   Chu, Bei Bei ^a   Ge, Liang ^a   Li, Bo Liang ^a   Yan, Yan ^b   Song, Bao Liang ^a  

^a INSTITUTE OF BIOCHEMISTRY AND CELL BIOLOGY   (China)

^b FUDAN UNIVERSITY   (China)

Author keywords

Ezetimibe; Niemann Pick C1 Like 1; NPC1; SSD

Indexed keywords

CHOLESTEROL; EZETIMIBE; FILIPIN; GLUCURONIDE; MEMBRANE PROTEIN; NIEMANN PICK C1 LIKE 1 PROTEIN; PROTEIN NPC1L1; PROTEINASE; TRYPSIN; UNCLASSIFIED DRUG; AZETIDINE DERIVATIVE; EPITOPE; EZETIMIBE GLUCURONIDE; HYBRID PROTEIN; HYPOCHOLESTEROLEMIC AGENT; NPC1L1 PROTEIN, HUMAN;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANIMAL CELL CULTURE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL PERMEABILIZATION; CHOLESTEROL METABOLISM; CONTROLLED STUDY; CYTOPLASM; GENETIC TRANSFECTION; HUMAN; IMMUNOFLUORESCENCE; IN VIVO STUDY; INTERNALIZATION; LIPID ABSORPTION; MEMBRANE STRUCTURE; NONHUMAN; PHARMACOLOGICAL BLOCKING; PLASMID; PRIORITY JOURNAL; AMINO ACID SEQUENCE; ANIMAL; BIOLOGICAL MODEL; CELL MEMBRANE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; PROTEIN MOTIF; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; PROTEIN TRANSPORT; RAT; TRANSPORT AT THE CELLULAR LEVEL; TUMOR CELL LINE;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; ANIMALS; ANTICHOLESTEREMIC AGENTS; AZETIDINES; BIOLOGICAL TRANSPORT; CELL LINE, TUMOR; CELL MEMBRANE; CHOLESTEROL; CONSERVED SEQUENCE; EPITOPES; GLUCURONIDES; HUMANS; MEMBRANE PROTEINS; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; RATS; RECOMBINANT FUSION PROTEINS; TRANSFECTION;

EID: 69449089892     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M800669-JLR200     Document Type: Article

References (33)

1. Dietschy, J. M., S. D. Turley, and D. K. Spady. 1993. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J. Lipid Res. 34: 1637-1659.
2. Grundy, S. M. 1990. Cholesterol and coronary heart disease. Future directions. JAMA. 264: 3053-3059.
3. Lo, S. G., M. Petruzzelli, and A. Moschetta. 2008. A translational view on the biliary lipid secretory network. Biochim. Biophys. Acta. 1781: 79-96.
4. Goldstein, J. L., R. A. Bose-Boyd, and M. S. Brown. 2006. Protein sensors for membrane sterols. Cell. 124: 35-46.
5. Temel, R. E., W. Tang, Y. Ma, L. L. Rudel, M. C. Willingham, Y. A. Ioannou, J. P. Davies, L. M. Nilsson, and L. Yu. 2007. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J. Clin. Invest. 117: 1968-1978.
6. Altmann, S. W., H. R. Davis, Jr., L. J. Zhu, X. Yao, L. M. Hoos, G. Tetzloff, S. P. Iyer, M. Maguire, A. Golovko, M. Zeng, et al. 2004. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 303: 1201-1204.
7. Davis, H. R., Jr., L. J. Zhu, L. M. Hoos, G. Tetzloff, M. Maguire, J. Liu, X. Yao, S. P. Iyer, M. H. Lam, E. G. Lund, et al. 2004. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J. Biol. Chem. 279: 33586-33592.
8. Davies, J. P., B. Levy, and Y. A. Ioannou. 2000. Evidence for a Niemann-pick C (NPC) gene family: identification and characterization of NPC1L1. Genomics. 65: 137-145.
9. Davies, J. P., C. Scott, K. Oishi, A. Liapis, and Y. A. Ioannou. 2005. Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. J. Biol. Chem. 280: 12710-12720.
10. Sane, A. T., D. Sinnett, E. Delvin, M. Bendayan, V. Marcil, D. Menard, J. F. Beaulieu, and E. Levy. 2006. Localization and role of NPC1L1 in cholesterol absorption in human intestine. J. Lipid Res. 47: 2112-2120.
11. Kuhlencordt, P. J., P. Padmapriya, S. Rutzel, J. Schodel, K. Hu, A. Schafer, P. L. Huang, G. Ertl, and J. Bauersachs. 2008. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice. Atherosclerosis. 202: 48-57.
12. Garcia-Calvo, M., J. Lisnock, H. G. Bull, B. E. Hawes, D. A. Burnett, M. P. Braun, J. H. Crona, H. R. Davis, Jr., D. C. Dean, P. A. Detmers, et al. 2005. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc. Natl. Acad. Sci. USA. 102: 8132-8137.
13. Weinglass, A. B., M. Kohler, U. Schulte, J. Liu, E. O. Nketiah, A. Thomas, W. Schmalhofer, B. Williams, W. Bildl, D. R. McMasters, et al. 2008. Extracellular loop C of NPC1L1 is important for binding to ezetimibe. Proc. Natl. Acad. Sci. USA. 105: 11140-11145.
14. Ge, L., J. Wang, W. Qi, H. H. Miao, J. Cao, Y. X. Qu, B. L. Li, and B. L. Song. 2008. The cholesterol absorption inhibitor ezetimibe acts by blocking the sterol-induced internalization of NPC1L1. Cell Metab. 7: 508-519.
15. Chang, T. Y., and C. Chang. 2008. Ezetimibe blocks internalization of the NPC1L1/cholesterol complex. Cell Metab. 7: 469-471.
16. Yu, L., S. Bharadwaj, J. M. Brown, Y. Ma, W. Du, M. A. Davis, P. Michaely, P. Liu, M. C. Willingham, and L. L. Rudel. 2006. Cholesterol-regulated translocation of NPC1L1 to the cell surface facilitates free cholesterol uptake. J. Biol. Chem. 281: 6616-6624.
17. Loftus, S. K., J. A. Morris, E. D. Carstea, J. Z. Gu, C. Cummings, A. Brown, J. Ellison, K. Ohno, M. A. Rosenfeld, D. A. Tagle, et al. 1997. Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene. Science. 277: 232-235.
18. Chang, T. Y., P. C. Reid, S. Sugii, N. Ohgami, J. C. Cruz, and C. C. Chang. 2005. Niemann-Pick type C disease and intracellular cholesterol trafficking. J. Biol. Chem. 280: 20917-20920.
19. Kuwabara, P. E., and M. Labouesse. 2002. The sterol-sensing domain: multiple families, a unique role? Trends Genet. 18: 193-201.
20. Davies, J. P., and Y. A. Ioannou. 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: 24367-24374.
21. Nohturfft, A., M. S. Brown, and J. L. Goldstein. 1998. Topology of SREBP cleavage-activating protein, a polytopic membrane protein with a sterol-sensing domain. J. Biol. Chem. 273: 17243-17250.
22. Olender, E. H., and R. D. Simon. 1992. The intracellular targeting and membrane topology of 3-hydroxy-3-methylglutaryl-CoA reductase. J. Biol. Chem. 267: 4223-4235.
23. Cao, J., J. Wang, W. Qi, H. H. Miao, J. Wang, L. Ge, R. A. Bose-Boyd, J. J. Tang, B. L. Li, and B. L. Song. 2007. Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase. Cell Metab. 6: 115-128.
24. Feramisco, J. D., J. L. Goldstein, and M. S. Brown. 2004. Membrane topology of human insig-1, a protein regulator of lipid synthesis. J. Biol. Chem. 279: 8487-8496.
25. Clader, J. W. 2004. The discovery of ezetimibe: a view from outside the receptor. J. Med. Chem. 47: 1-9.
26. Van Heek, M., C. F. France, D. S. Compton, R. L. McLeod, N. P. Yumibe, K. B. Alton, E. J. Sybertz, and H. R. Davis, Jr. 1997. In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J. Pharmacol. Exp. Ther. 283: 157-163.
27. Harris, M., W. Davis, and W. V. Brown. 2003. Ezetimibe. Drugs Today (Barc.). 39: 229-247.
28. Song, B. L., N. Sever, and R. A. Bose-Boyd. 2005. Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Mol. Cell. 19: 829-840.
29. Sever, N., T. Yang, M. S. Brown, J. L. Goldstein, and R. A. Bose-Boyd. 2003. Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Mol. Cell. 11: 25-33.
30. Yang, T., P. J. Espenshade, M. E. Wright, D. Yabe, Y. Gong, R. Aebersold, J. L. Goldstein, and M. S. Brown. 2002. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 110: 489-500.
31. Ohgami, N., D. C. Ko, M. Thomas, M. P. Scott, C. C. Chang, and T. Y. Chang. 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: 12473-12478.
32. Infante, R. E., L. Abi-Mosleh, A. Radhakrishnan, J. D. Dale, M. S. Brown, and J. L. Goldstein. 2008. Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein. J. Biol. Chem. 283: 1052-1063.
33. R. E. Infante, A. Radhakrishnan, L. Abi-Mosleh, L. N. Kinch, M. L. Wang, N. V. Grishin, J. L. Goldstein, and M. S. Brown. 2008. Purified NPC1 protein: II. Localization of sterol binding to a 240-amino acid soluble luminal loop. J. Biol. Chem. 283: 1064-1075.