Plasma membrane tetraspanin CD81 complexes with proprotein convertase subtilisin/kexin type 9 (PCSK9) and low density lipoprotein receptor (LDLR), and Its levels are reduced by PCSK9

Journal of Biological Chemistry

Volumn 290, Issue 38, 2015, Pages 23385-23400

  Le, Quoc Tuan ^a,b   Blanchet, Matthieu ^a   Seidah, Nabil G ^c   Labonté, Patrick ^a  

^a INRS INSTITUT ARMAND FRAPPIER   (Canada)

^b VIETNAM MILITARY MEDICAL UNIVERSITY   (Viet Nam)

^c CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMISTRY; BIOLOGY;

FUNCTIONAL INTERACTION; LOW DENSITY LIPOPROTEIN RECEPTORS; STRUCTURE-BASED; SUBTILISIN; TETRASPANIN;

CELL MEMBRANES;

CD81 ANTIGEN; LOW DENSITY LIPOPROTEIN RECEPTOR; PROTEIN PCSK9; SERINE PROTEINASE; UNCLASSIFIED DRUG; CD81 PROTEIN, HUMAN; LDLR PROTEIN, HUMAN; MULTIPROTEIN COMPLEX; PCSK9 PROTEIN, HUMAN;

AMINO TERMINAL SEQUENCE; ARTICLE; BIOASSAY; CARBOXY TERMINAL SEQUENCE; CELL LINE; CELL SURFACE; COMPLEX FORMATION; CONTROLLED STUDY; GAIN OF FUNCTION MUTATION; HUMAN; HUMAN CELL; IMMUNOCHEMISTRY; IMMUNOPRECIPITATION; LOSS OF FUNCTION MUTATION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN INTERACTION; REGULATORY MECHANISM; STRUCTURE ACTIVITY RELATION; AMINO ACID SUBSTITUTION; ANIMAL; BIOSYNTHESIS; CHO CELL LINE; CRICETULUS; GENE EXPRESSION REGULATION; GENETICS; HAMSTER; METABOLISM; MISSENSE MUTATION; PHYSIOLOGY;

AMINO ACID SUBSTITUTION; ANIMALS; ANTIGENS, CD81; CHO CELLS; CRICETINAE; CRICETULUS; GENE EXPRESSION REGULATION; HUMANS; MULTIPROTEIN COMPLEXES; MUTATION, MISSENSE; PROPROTEIN CONVERTASES; PROTEOLYSIS; RECEPTORS, LDL; SERINE ENDOPEPTIDASES;

EID: 84942878498     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.642991     Document Type: Article

References (60)

1. Seidah, N. G., Benjannet, S., Wickham, L., Marcinkiewicz, J., Jasmin, S. B., Stifani, S., Basak, A., Prat, A., and Chretien, M. (2003) The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. U.S.A. 100, 928-933
2. Abifadel, M., Varret, M., Rabès, J. P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derré, A., Villéger, L., Farnier, M., Beucler, I., Bruckert, E., Chambaz, J., Chanu, B., Lecerf, J. M., Luc, G., Moulin, P., Weissenbach, J., Prat, A., Krempf, M., Junien, C., Seidah, N. G., and Boileau, C. (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34, 154-156
3. Zaid, A., Roubtsova, A., Essalmani, R., Marcinkiewicz, J., Chamberland, A., Hamelin, J., Tremblay, M., Jacques, H., Jin, W., Davignon, J., Seidah, N. G., and Prat, A. (2008) Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology 48, 646-654
4. Maxwell, K. N., and Breslow, J. L. (2004) Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc. Natl. Acad. Sci. U.S.A. 101, 7100-7105
5. Benjannet, S., Rhainds, D., Essalmani, R., Mayne, J., Wickham, L., Jin, W., Asselin, M. C., Hamelin, J., Varret, M., Allard, D., Trillard, M., Abifadel, M., Tebon, A., Attie, A. D., Rader, D. J., Boileau, C., Brissette, L., Chrétien, M., Prat, A., and Seidah, N. G. (2004) NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J. Biol. Chem. 279, 48865-48875
6. Seidah, N. G., Awan, Z., Chrétien, M., and Mbikay, M. (2014) PCSK9: a key modulator of cardiovascular health. Circ. Res. 114, 1022-1036
7. Seidah, N. G., and Prat, A. (2012) The biology and therapeutic targeting of the proprotein convertases. Nat. Rev. Drug Discov. 11, 367-383
8. Roubtsova, A., Munkonda, M. N., Awan, Z., Marcinkiewicz, J., Chamberland, A., Lazure, C., Cianflone, K., Seidah, N. G., and Prat, A. (2011) Circulating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue. Arterioscler. Thromb. Vasc. Biol. 31, 785-791
9. Poirier, S., Mayer, G., Benjannet, S., Bergeron, E., Marcinkiewicz, J., Nassoury, N., Mayer, H., Nimpf, J., Prat, A., and Seidah, N. G. (2008) The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J. Biol. Chem. 283, 2363-2372
10. Kwon, H. J., Lagace, T. A., McNutt, M. C., Horton, J. D., and Deisenhofer, J. (2008) Molecular basis for LDL receptor recognition by PCSK9. Proc. Natl. Acad. Sci. U.S.A. 105, 1820-1825
11. Zhang, D. W., Lagace, T. A., Garuti, R., Zhao, Z., McDonald, M., Horton, J. D., Cohen, J. C., and Hobbs, H. H. (2007) Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeatAof low density lipoprotein receptor decreases receptor recycling and increases degradation. J. Biol. Chem. 282, 18602-18612
12. Nassoury, N., Blasiole, D. A., Tebon Oler, A., Benjannet, S., Hamelin, J., Poupon, V., McPherson, P. S., Attie, A. D., Prat, A., and Seidah, N. G. (2007) The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic 8, 718-732
13. Yamamoto, T., Lu, C., and Ryan, R. O. (2011) A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor. J. Biol. Chem. 286, 5464-5470
14. Abifadel, M., Guerin, M., Benjannet, S., Rabès, J. P., Le Goff, W., Julia, Z., Hamelin, J., Carreau, V., Varret, M., Bruckert, E., Tosolini, L., Meilhac, O., Couvert, P., Bonnefont-Rousselot, D., Chapman, J., Carrié, A., Michel, J. B., Prat, A., Seidah, N. G., and Boileau, C. (2012) Identification and characterization of new gain-of-function mutations in the PCSK9 gene responsible for autosomal dominant hypercholesterolemia. Atherosclerosis 223, 394-400
15. Lo Surdo, P., Bottomley, M. J., Calzetta, A., Settembre, E. C., Cirillo, A., Pandit, S., Ni, Y. G., Hubbard, B., Sitlani, A., and Carfí, A. (2011) Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. 12, 1300-1305
16. Poirier, S., Mayer, G., Poupon, V., McPherson, P. S., Desjardins, R., Ly, K., Asselin, M. C., Day, R., Duclos, F. J., Witmer, M., Parker, R., Prat, A., and Seidah, N. G. (2009) Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route. J. Biol. Chem. 284, 28856-28864
17. Abifadel, M., Rabès, J. P., Devillers, M., Munnich, A., Erlich, D., Junien, C., Varret, M., and Boileau, C. (2009) Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum. Mutat. 30, 520-529
18. Cameron, J., Holla, O. L., Laerdahl, J. K., Kulseth, M. A., Ranheim, T., Rognes, T., Berge, K. E., and Leren, T. P. (2008) Characterization of novel mutations in the catalytic domain of the PCSK9 gene. J. Intern. Med. 263, 420-431
19. Fasano, T., Sun, X. M., Patel, D. D., and Soutar, A. K. (2009) Degradation of LDLR protein mediated by 'gain of function' PCSK9 mutants in normal and ARH cells. Atherosclerosis 203, 166-171
20. Fisher, T. S., Lo Surdo, P., Pandit, S., Mattu, M., Santoro, J. C., Wisniewski, D., Cummings, R. T., Calzetta, A., Cubbon, R. M., Fischer, P. A., Tarachandani, A., De Francesco, R., Wright, S. D., Sparrow, C. P., Carfi, A., and Sitlani, A. (2007) Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation. J. Biol. Chem. 282, 20502-20512
21. Labonté, P., Begley, S., Guévin, C., Asselin, M. C., Nassoury, N., Mayer, G., Prat, A., and Seidah, N. G. (2009) PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression. Hepatology 50, 17-24
22. Bolte, S., and Cordelières, F. P. (2006) A guided tour into subcellular colocalization analysis in light microscopy. J. Microsc. 224, 213-232
23. Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., and Horton, J. D. (2006) Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J. Clin. Investig. 116, 2995-3005
24. Miyake, Y., Kimura, R., Kokubo, Y., Okayama, A., Tomoike, H., Yamamura, T., and Miyata, T. (2008) Genetic variants in PCSK9 in the Japanese population: rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population. Atherosclerosis 196, 29-36
25. Noguchi, T., Katsuda, S., Kawashiri, M. A., Tada, H., Nohara, A., Inazu, A., Yamagishi, M., Kobayashi, J., and Mabuchi, H. (2010) The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation. Atherosclerosis 210, 166-172
26. Mayer, G., Poirier, S., and Seidah, N. G. (2008) Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J. Biol. Chem. 283, 31791-31801
27. Homer, V. M., Marais, A. D., Charlton, F., Laurie, A. D., Hurndell, N., Scott, R., Mangili, F., Sullivan, D. R., Barter, P. J., Rye, K. A., George, P. M., and Lambert, G. (2008) Identification and characterization of two nonsecreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa. Atherosclerosis 196, 659-666
28. Bottomley, M. J., Cirillo, A., Orsatti, L., Ruggeri, L., Fisher, T. S., Santoro, J. C., Cummings, R. T., Cubbon, R. M., Lo Surdo, P., Calzetta, A., Noto, A., Baysarowich, J., Mattu, M., Talamo, F., De Francesco, R., Sparrow, C. P., Sitlani, A., and Carfí, A. (2009) Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants. J. Biol. Chem. 284, 1313-1323
29. Benjannet, S., Rhainds, D., Hamelin, J., Nassoury, N., and Seidah, N. G. (2006) The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and posttranslational modifications. J. Biol. Chem. 281, 30561-30572
30. Allard, D., Amsellem, S., Abifadel, M., Trillard, M., Devillers, M., Luc, G., Krempf, M., Reznik, Y., Girardet, J. P., Fredenrich, A., Junien, C., Varret, M., Boileau, C., Benlian, P., and Rabès, J. P. (2005) Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia. Hum. Mutat. 26, 497
31. Bourbon, M., Alves, A. C., Medeiros, A. M., Silva, S., Soutar, A. K., and Investigators of Portuguese FH Study (2008) Familial hypercholesterolaemia in Portugal. Atherosclerosis 196, 633-642
32. Leren, T. P. (2004) Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin. Genet. 65, 419-422
33. Cunningham, D., Danley, D. E., Geoghegan, K. F., Griffor, M. C., Hawkins, J. L., Subashi, T. A., Varghese, A. H., Ammirati, M. J., Culp, J. S., Hoth, L. R., Mansour, M. N., McGrath, K. M., Seddon, A. P., Shenolikar, S., Stutzman- Engwall, K. J., Warren, L. C., Xia, D., and Qiu, X. (2007) Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat. Struct. Mol. Biol. 14, 413-419
34. Kotowski, I. K., Pertsemlidis, A., Luke, A., Cooper, R. S., Vega, G. L., Cohen, J. C., and Hobbs, H. H. (2006) A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am. J. Hum. Genet. 78, 410-422
35. Pisciotta, L., Priore Oliva, C., Cefalù, A. B., Noto, D., Bellocchio, A., Fresa, R., Cantafora, A., Patel, D., Averna, M., Tarugi, P., Calandra, S., and Bertolini, S. (2006) Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia. Atherosclerosis 186, 433-440
36. Dubuc, G., Tremblay, M., Paré, G., Jacques, H., Hamelin, J., Benjannet, S., Boulet, L., Genest, J., Bernier, L., Seidah, N. G., and Davignon, J. (2010) A new method for measurement of total plasma PCSK9: clinical applications. J. Lipid Res. 51, 140-149
37. Cameron, J., Holla, Ø. L., Laerdahl, J. K., Kulseth, M. A., Berge, K. E., and Leren, T. P. (2009) Mutation S462P in the PCSK9 gene reduces secretion of mutant PCSK9 without affecting the autocatalytic cleavage. Atherosclerosis 203, 161-165
38. Fasano, T., Cefalù, A. B., Di Leo, E., Noto, D., Pollaccia, D., Bocchi, L., Valenti, V., Bonardi, R., Guardamagna, O., Averna, M., and Tarugi, P. (2007) A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler. Thromb. Vasc. Biol. 27, 677-681
39. Canuel, M., Sun, X., Asselin, M. C., Paramithiotis, E., Prat, A., and Seidah, N. G. (2013) Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1). PLoS One 8, e64145
40. Lippincott-Schwartz, J., and Fambrough, D. M. (1987) Cycling of the integral membrane glycoprotein, LEP100, between plasma membrane and lysosomes: kinetic and morphological analysis. Cell 49, 669-677
41. Urban, D., Pöss, J., Böhm, M., and Laufs, U. (2013) Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J. Am. Coll. Cardiol. 62, 1401-1408
42. Blokzijl, A., Nong, R., Darmanis, S., Hertz, E., Landegren, U., and Kamali- Moghaddam, M. (2014) Protein biomarker validation via proximity ligation assays. Biochim. Biophys. Acta 1844, 933-939
43. Söderberg, O., Leuchowius, K. J., Gullberg, M., Jarvius, M., Weibrecht, I., Larsson, L. G., and Landegren, U. (2008) Characterizing proteins and their interactions in cells and tissues using the in situ proximity ligation assay. Methods 45, 227-232
44. Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K. J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L. G., and Landegren, U. (2006) Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat. Methods 3, 995-1000
45. Sun, H., Samarghandi, A., Zhang, N., Yao, Z., Xiong, M., and Teng, B. B. (2012) Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor. Arterioscler. Thromb. Vasc. Biol. 32, 1585-1595
46. Huang, W., Febbraio, M., and Silverstein, R. L. (2011) CD9 tetraspanin interacts with CD36 on the surface of macrophages: a possible regulatory influence on uptake of oxidized low density lipoprotein. PLoS One 6, e29092
47. Krieger, M., Brown, M. S., and Goldstein, J. L. (1981) Isolation of Chinese hamster cell mutants defective in the receptor-mediated endocytosis of low density lipoprotein. J. Mol. Biol. 150, 167-184
48. Hemler, M. E. (2005) Tetraspanin functions and associated microdomains. Nat. Rev. Mol. Cell Biol. 6, 801-811
49. Horváth, G., Serru, V., Clay, D., Billard, M., Boucheix, C., and Rubinstein, E. (1998) CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82. J. Biol. Chem. 273, 30537-30543
50. Strøm, T. B., Holla, Ø. L., Tveten, K., Cameron, J., Berge, K. E., and Leren, T. P. (2010) Disrupted recycling of the low density lipoprotein receptor by PCSK9 is not mediated by residues of the cytoplasmic domain. Mol. Genet. Metab. 101, 76-80
51. Saavedra, Y. G., Day, R., and Seidah, N. G. (2012) The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway. J. Biol. Chem. 287, 43492-43501
52. Zhang, D. W., Garuti, R., Tang, W. J., Cohen, J. C., and Hobbs, H. H. (2008) Structural requirements for PCSK9-mediated degradation of the lowdensity lipoprotein receptor. Proc. Natl. Acad. Sci. U.S.A. 105, 13045-13050
53. Butkinaree, C., Canuel, M., Essalmani, R., Poirier, S., Benjannet, S., Asselin, M. C., Roubtsova, A., Hamelin, J., Marcinkiewicz, J., Chamberland, A., Guillemot, J., Mayer, G., Sisodia, S. S., Jacob, Y., Prat, A., and Seidah, N. G. (2015) Amyloid precursor-like protein 2 and sortilin do not regulate the PCSK9 convertase-mediated low density lipoprotein receptor degradation but interact with each other. J. Biol. Chem. 290, 18609-18620
54. Pileri, P., Uematsu, Y., Campagnoli, S., Galli, G., Falugi, F., Petracca, R., Weiner, A. J., Houghton, M., Rosa, D., Grandi, G., and Abrignani, S. (1998) Binding of hepatitis C virus to CD81. Science 282, 938-941
55. Akazawa, D., Date, T., Morikawa, K., Murayama, A., Miyamoto, M., Kaga, M., Barth, H., Baumert, T. F., Dubuisson, J., and Wakita, T. (2007) CD81 expression is important for the permissiveness of Huh7 cell clones for heterogeneous hepatitis C virus infection. J. Virol. 81, 5036-5045
56. Albecka, A., Belouzard, S., Op de Beeck, A., Descamps, V., Goueslain, L., Bertrand-Michel, J., Tercé, F., Duverlie, G., Rouillé, Y., and Dubuisson, J. (2012) Role of low-density lipoprotein receptor in the hepatitis C virus life cycle. Hepatology 55, 998-1007
57. Fénéant, L., Levy, S., and Cocquerel, L. (2014) CD81 and hepatitis C virus (HCV) infection. Viruses 6, 535-572
58. Harris, H. J., Davis, C., Mullins, J. G., Hu, K., Goodall, M., Farquhar, M. J., Mee, C. J., McCaffrey, K., Young, S., Drummer, H., Balfe, P., and McKeating, J. A. (2010) Claudin association with CD81 defines hepatitis C virus entry. J. Biol. Chem. 285, 21092-21102
59. Evans, M. J., von Hahn, T., Tscherne, D. M., Syder, A. J., Panis, M., Wölk, B., Hatziioannou, T., McKeating, J. A., Bieniasz, P. D., and Rice, C. M. (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446, 801-805
60. Seidah, N. G., Poirier, S., Denis, M., Parker, R., Miao, B., Mapelli, C., Prat, A., Wassef, H., Davignon, J., Hajjar, K. A., and Mayer, G. (2012) Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS One 7, e41865