Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation

PLoS ONE

Volumn 7, Issue 7, 2012, Pages

  Seidah, Nabil G ^b   Poirier, Steve ^b   Denis, Maxime ^b   Parker, Rex ^c   Miao, Bowman ^c   Mapelli, Claudio ^c   Prat, Annik ^b   Wassef, Hanny ^b   Davignon, Jean ^b   Hajjar, Katherine A ^d   Mayer, Gaétan ^a  

^a MONTREAL HEART INSTITUTE   (Canada)

^b CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^c BRISTOL MYERS SQUIBB   (United States)

^d WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; HIGH DENSITY LIPOPROTEIN; LIPOCORTIN 2; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9; SERINE PROTEINASE; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ADRENAL GLAND; ADULT; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; COLON; CONTROLLED STUDY; EXON; GENE SEQUENCE; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; LIPID METABOLISM; MALE; MOUSE; NONHUMAN; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; SINGLE NUCLEOTIDE POLYMORPHISM; WESTERN BLOTTING;

ADENOVIRIDAE; AMINO ACID SEQUENCE; ANIMALS; ANNEXIN A2; CELL LINE; CHOLESTEROL, LDL; CRICETINAE; EXONS; EXTRACELLULAR SPACE; HUMANS; LIVER; MALE; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; POLYMORPHISM, SINGLE NUCLEOTIDE; PROPROTEIN CONVERTASES; PROTEIN STRUCTURE, TERTIARY; PROTEOLYSIS; RECEPTORS, LDL; SERINE ENDOPEPTIDASES;

MUS;

EID: 84864413267     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0041865     Document Type: Article

References (82)

1. Varret M, Abifadel M, Rabes JP, Boileau C, (2008) Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet 73: 1-13.
2. Cenarro A, Garcia-Otin AL, Tejedor MT, Solanas M, Jarauta E, et al. (2011) A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22. Clin Genet 79: 475-481.
3. Marques-Pinheiro A, Marduel M, Rabès J-P, Devillers M, Villéger L, et al. (2010) A fourth locus for autosomal dominant hypercholesterolemia maps at 16q22.1. Eur J Hum Genet 18: 1236-1242.
4. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, et al. (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.
5. Seidah NG, Mayer G, Zaid A, Rousselet E, Nassoury N, et al. (2008) The activation and physiological functions of the proprotein convertases. Int J Biochem Cell Biol 40: 1111-1125.
6. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, et al. (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34: 154-156.
7. Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, et al. (2005) Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A 102: 5374-5379.
8. Maxwell KN, Breslow JL, (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.
9. Zaid A, Roubtsova A, Essalmani R, Marcinkiewicz J, Chamberland A, et al. (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.
10. Rousselet E, Marcinkiewicz J, Kriz J, Zhou A, Hatten ME, et al. (2011) PCSK9 reduces the protein levels of the LDL receptor in mouse brain during development and after ischemic stroke. J Lipid Res 52: 1383-1391.
11. Liu M, Wu G, Baysarowich J, Kavana M, Addona GH, et al. (2010) PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain. J Lipid Res 51: 2611-2618.
12. Cunningham D, Danley DE, Geoghegan KF, Griffor MC, Hawkins JL, et al. (2007) Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol 14: 413-419.
13. McNutt MC, Lagace TA, Horton JD, (2007) Catalytic Activity Is Not Required for Secreted PCSK9 to Reduce Low Density Lipoprotein Receptors in HepG2 Cells. J Biol Chem 282: 20799-20803.
14. Dubuc G, Tremblay M, Pare G, Jacques H, Hamelin J, et al. (2010) A new method for measurement of total plasma PCSK9: clinical applications. J Lipid Res 51: 140-149.
15. Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J, (2008) Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci U S A 105: 1820-1825.
16. Nassoury N, Blasiole DA, Tebon Oler A, Benjannet S, Hamelin J, et al. (2007) The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic 8: 718-732.
17. Zhang DW, Lagace TA, Garuti R, Zhao Z, McDonald M, et al. (2007) Binding of Proprotein Convertase Subtilisin/Kexin Type 9 to Epidermal Growth Factor-like Repeat A of Low Density Lipoprotein Receptor Decreases Receptor Recycling and Increases Degradation. J Biol Chem 282: 18602-18612.
18. Poirier S, Mayer G, Poupon V, McPherson PS, Desjardins R, et al. (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.
19. Li J, Tumanut C, Gavigan J-A, Huang W-J, Hampton Eric N, et al. (2007) Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem J 406: 203-207.
20. Benjannet S, Luna Saavedra YG, Hamelin J, Asselin MC, Essalmani R, et al. (2010) Effects of the prosegment and PH on the activity of PCSK9: evidence for additional processing events. J Biol Chem 285: 40965-40978.
21. Zhang DW, Garuti R, Tang WJ, Cohen JC, Hobbs HH, (2008) Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci U S A 105: 13045-13050.
22. Poirier S, Mayer G, Benjannet S, Bergeron E, Marcinkiewicz J, et al. (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.
23. Shan L, Pang L, Zhang R, Murgolo NJ, Lan H, et al. (2008) PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun 375: 69-73.
24. Roubtsova A, Munkonda MN, Awan Z, Marcinkiewicz J, Chamberland A, et al. (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.
25. Akram ON, Bernier A, Petrides F, Wong G, Lambert G, (2010) Beyond LDL Cholesterol, a New Role for PCSK9. Arterioscler Thromb Vasc Biol 30: 1279-1281.
26. Benjannet S, Rhainds D, Essalmani R, Mayne J, Wickham L, et al. (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.
27. Timms KM, Wagner S, Samuels ME, Forbey K, Goldfine H, et al. (2004) A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree. Hum Genet 114: 349-353.
28. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, et al. (2005) Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 37: 161-165.
29. Kotowski IK, Pertsemlidis A, Luke A, Cooper RS, Vega GL, et al. (2006) A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet 78: 410-422.
30. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH, (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354: 1264-1272.
31. Zhao Z, Tuakli-Wosornu Y, Lagace TA, Kinch L, Grishin NV, et al. (2006) Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 79: 514-523.
32. Hooper AJ, Marais AD, Tanyanyiwa DM, Burnett JR, (2007) The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 193: 445-448.
33. Seidah NG, (2009) PCSK9 as a therapeutic target of dyslipidemia. Expert Opin Ther Targets 13: 19-28.
34. Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, et al. (2009) 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult- 2009 recommendations. Can J Cardiol 25: 567-579.
35. Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, et al. (1993) SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci U S A 90: 11603-11607.
36. Brown MS, Goldstein JL, (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89: 331-340.
37. Steinberg D, (2006) Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part V: The discovery of the statins and the end of the controversy. J Lipid Res 47: 1339-1351.
38. Delahoy PJ, Magliano DJ, Webb K, Grobler M, Liew D, (2009) The relationship between reduction in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated meta-analysis. Clin Ther 31: 236-244.
39. Kones R, (2010) Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease-a perspective. Drug Des Devel Ther 4: 383-413.
40. Abd TT, Jacobson TA, (2011) Statin-induced myopathy: a review and update. Expert Opin Drug Saf 10: 373-387.
41. Dubuc G, Chamberland A, Wassef H, Davignon J, Seidah NG, et al. (2004) Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 24: 1454-1459.
42. Attie AD, Seidah NG, (2005) Dual regulation of the LDL receptor-Some clarity and new questions. Cell Metab 1: 290-292.
43. Thompson JF, Hyde CL, Wood LS, Paciga SA, Hinds DA, et al. (2009) Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circ Cardiovasc Genet 2: 173-181.
44. Naoumova RP, Tosi I, Patel D, Neuwirth C, Horswell SD, et al. (2005) Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response. Arterioscler Thromb Vasc Biol 25: 2654-2660.
45. Berge KE, Ose L, Leren TP, (2006) Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy. Arterioscler Thromb Vasc Biol 26: 1094-1100.
46. Graham MJ, Lemonidis KM, Whipple CP, Subramaniam A, Monia BP, et al. (2007) Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res 48: 763-767.
47. Frank-Kamenetsky M, Grefhorst A, Anderson NN, Racie TS, Bramlage B, et al. (2008) Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci U S A 105: 11915-11920.
48. Gupta N, Fisker N, Asselin MC, Lindholm M, Rosenbohm C, et al. (2010) A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo. PLoS One 5: e10682.
49. Dias C, Shaywitz A, Cooke B, Uy S, Emery M, et al. (2012) EFFECTS OF AMG 145, A FULLY HUMAN MONOCLONAL ANTIBODY AGAINST PCSK9, ON LOW-DENSITY LIPOPROTEIN CHOLESTEROL IN SUBJECTS TAKING STATINS: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ASCENDING MULTIPLE-DOSE STUDY. J Am Coll Cardiol 59: E1379-.
50. Ni YG, Di Marco S, Condra JH, Peterson LB, Wang W, et al. (2011) A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo. J Lipid Res 52: 78-86.
51. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, et al. (2012) Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol. N Engl J Med 366: 1108-1118.
52. Chan JC, Piper DE, Cao Q, Liu D, King C, et al. (2009) A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci U S A 106: 9820-9825.
53. Seidah NG, Prat A, (2012) The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov advance online publication.
54. Mayer G, Poirier S, Seidah NG, (2008) Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem 283: 31791-31801.
55. Waisman DM, (1995) Annexin II tetramer: structure and function. Mol Cell Biochem 149-150: 301-322.
56. Deora AB, Kreitzer G, Jacovina AT, Hajjar KA, (2004) An Annexin 2 Phosphorylation Switch Mediates p11-dependent Translocation of Annexin 2 to the Cell Surface. J Biol Chem 279: 43411-43418.
57. Chung CY, Erickson HP, (1994) Cell surface annexin II is a high affinity receptor for the alternatively spliced segment of tenascin-C. J Cell Biol 126: 539-548.
58. Patchell BJ, Wojcik KR, Yang TL, White SR, Dorscheid DR, (2007) Glycosylation and annexin II cell surface translocation mediate airway epithelial wound repair. Am J Physiol Lung Cell Mol Physiol 293: L354-363.
59. Cesarman GM, Guevara CA, Hajjar KA, (1994) An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J Biol Chem 269: 21198-21203.
60. Flood EC, Hajjar KA, (2011) The annexin A2 system and vascular homeostasis. Vascul Pharmacol 54: 59-67.
61. Ling Q, Jacovina AT, Deora A, Febbraio M, Simantov R, et al. (2004) Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo. J Clin Invest 113: 38-48.
62. Ni YG, Condra JH, Orsatti L, Shen X, Di Marco S, et al. (2010) A Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) C-terminal Domain Antibody Antigen-binding Fragment Inhibits PCSK9 Internalization and Restores Low Density Lipoprotein Uptake. J Biol Chem 285: 12882-12891.
63. Grefhorst A, McNutt MC, Lagace TA, Horton JD, (2008) Plasma PCSK9 preferentially reduces liver LDL receptors in mice. J Lipid Res 49: 1303-1311.
64. Nour N, Mayer G, Mort JS, Salvas A, Mbikay M, et al. (2005) The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases. Mol Biol Cell 16: 5215-5226.
65. Mayer G, Boileau G, Bendayan M, (2004) Sorting of furin in polarized epithelial and endothelial cells: expression beyond the Golgi apparatus. J Histochem Cytochem 52: 567-579.
66. Schmidt RJ, Beyer TP, Bensch WR, Qian Y-W, Lin A, et al. (2008) Secreted proprotein convertase subtilisin/kexin type 9 reduces both hepatic and extrahepatic low-density lipoprotein receptors in vivo. Biochem Biophys Res Commun 370: 634-640.
67. Luo Y, Warren L, Xia D, Jensen H, Sand T, et al. (2009) Function and distribution of circulating human PCSK9 expressed extrahepatically in transgenic mice. J Lipid Res 50: 1581-1588.
68. Benjannet S, Rhainds D, Hamelin J, Nassoury N, Seidah NG, (2006) The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem 281: 30561-30572.
69. Mayer G, Hamelin J, Asselin MC, Pasquato A, Marcinkiewicz E, et al. (2008) The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates. J Biol Chem 283: 2373-2384.
70. Mayer G, Boileau G, Bendayan M, (2003) Furin interacts with proMT1-MMP and integrin alphaV at specialized domains of renal cell plasma membrane. J Cell Sci 116: 1763-1773.
71. Mayer G, Boileau G, Bendayan M, (2004) The proprotein convertase furin colocalizes with caveolin-1 in the Golgi apparatus and endosomes of hepatocytes. Cell Tissue Res 316: 55-63.
72. Essalmani R, Susan-Resiga D, Chamberland A, Abifadel M, Creemers JW, et al. (2011) In vivo evidence that furin from hepatocytes inactivates PCSK9. J Biol Chem 286: 4257-4263.
73. Horton JD, Cohen JC, Hobbs HH, (2009) PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res 50 (Suppl): S172-177.
74. Brown MS, Goldstein JL, (2006) Biomedicine. Lowering LDL-not only how low, but how long? Science 311: 1721-1723.
75. Crunkhorn S, (2011) Trial watch: PCSK9 antibody reduces LDL cholesterol. Nat Rev Drug Discov 11: 11.
76. Kraemer FB, (2007) Adrenal cholesterol utilization. Mol Cell Endocrinol 265-266: 42-45.
77. Carr BR, Simpson ER, (1981) Lipoprotein utilization and cholesterol synthesis by the human fetal adrenal gland. Endocr Rev 2: 306-326.
78. Lucki NC, Li D, Sewer MB, (2012) Sphingosine-1-phosphate rapidly increases cortisol biosynthesis and the expression of genes involved in cholesterol uptake and transport in H295R adrenocortical cells. Mol Cell Endocrinol 348: 165-175.
79. Du F, Hui Y, Zhang M, Linton MF, Fazio S, et al. (2011) Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J Biol Chem 286: 43054-43061.
80. Surdo PL, Bottomley MJ, Calzetta A, Settembre EC, Cirillo A, et al. (2011) Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep 12: 1300-1305.
81. Zelcer N, Hong C, Boyadjian R, Tontonoz P, (2009) LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science 325: 100-104.
82. Saris CJ, Kristensen T, D'Eustachio P, Hicks LJ, Noonan DJ, et al. (1987) cDNA sequence and tissue distribution of the mRNA for bovine and murine p11, the S100-related light chain of the protein-tyrosine kinase substrate p36 (calpactin I). J Biol Chem 262: 10663-10671.