Internalized PCSK9 dissociates from recycling LDL receptors in PCSK9-resistant SV-589 fibroblasts

Journal of Lipid Research

Volumn 55, Issue 2, 2014, Pages 266-275

  Nguyen, My Anh ^a   Kosenko, Tanja ^a   Lagace, Thomas A ^a  

^a UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

Author keywords

Degradation; Endosome; Ligand dissociation

Indexed keywords

DEGRADATION; ENDOSOME; LIGAND DISSOCIATION;

CELL LINE; ENDOCYTOSIS; FIBROBLASTS; HUMANS; INTRACELLULAR SPACE; LYSOSOMES; MUTATION; PROPROTEIN CONVERTASES; PROTEIN TRANSPORT; PROTEOLYSIS; RECEPTORS, LDL; SERINE ENDOPEPTIDASES; SKIN; STEROLS;

EID: 84893355049     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M044156     Document Type: Article

References (59)

1. Goldstein, J. L., and M. S. Brown.2009.The LDL receptor. Arterioscler. Thromb. Vasc. Biol. 29 : 431-438.
2. Rudenko, G., L. Henry, K. Henderson, K. Ichtchenko, M. S. Brown, J. L. Goldstein, and J. Deisenhofer.2002.Structure of the LDL receptor extracellular domain at endosomal pH. Science.298 : 2353-2358.
3. Rudenko, G., and J. Deisenhofer.2003.The low-density lipoprotein receptor: ligands, debates and lore. Curr. Opin. Struct. Biol. 13 : 683-689
4. Brown, M. S., and J. L. Goldstein.1981.Lowering plasma cholesterol by raising LDL receptors.N. Engl. J. Med. 305 : 515-517.
5. Lagace, T. A., D. E. Curtis, R. Garuti, M. C. McNutt, S. W. Park, H. B. Prather, N. N. Anderson, Y. K. Ho, R. E. Hammer, and J. D. Horton.2006.Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J. Clin. Invest. 116 : 2995-3005.
6. Lambert, G., B. Sjouke, B. Choque, J. J. Kastelein, and G. K. Hovingh.2012.The PCSK9 decade. J. Lipid Res. 53 : 2515-2524.
7. Seidah, N. G., and A. Prat.2012.The biology and therapeutic targeting of the proprotein convertases. Nat. Rev. Drug Discov. 11 : 367-383.
8. Benjannet, S., D. Rhainds, R. Essalmani, J. Mayne, L. Wickham, W. Jin, M. C. Asselin, J. Hamelin, M. Varret, D. Allard, 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.
9. Zhang, D-W., T. A. Lagace, R. Garuti, Z. Zhao, M. McDonald, J. D. Horton, J. C. Cohen, and H. H. Hobbs.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.
10. Lambert, G., F. Charlton, K. A. Rye, and D. E. Piper.2009.Molecular basis of PCSK9 function. Atherosclerosis.203 : 1-7.
11. Horton, J. D., J. C. Cohen, and H. H. Hobbs.2009.PCSK9: a convertase that coordinates LDL catabolism. J. Lipid Res. 50 (Suppl.) : S172-S177.
12. Cunningham, D., D. E. Danley, K. F. Geoghegan, M. C. Griffor, J. L. Hawkins, T. A. Subashi, A. H. Varghese, M. J. Ammirati, J. S. Culp, L. R. Hoth, et al.2007.Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat. Struct. Mol. Biol. 14 : 413-419.
13. Piper, D. E., S. Jackson, Q. Liu, W. G. Romanow, S. Shetterly, S. T. Thibault, B. Shan, and N. P. Walker.2007.The crystal structure of PCSK9: A regulator of plasma LDL-cholesterol. Structure.15 : 545-552.
14. Abifadel, M., M. Varret, J. P. Rabes, D. Allard, K. Ouguerram, M. Devillers, C. Cruaud, S. Benjannet, L. Wickham, D. Erlich, et al.2003.Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34 : 154-156.
15. Abifadel, M., J. P. Rabes, M. Devillers, A. Munnich, D. Erlich, C. Junien, M. Varret, and C. Boileau.2009.Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum. Mutat. 30 : 520-529.
16. Naoumova, R. P., I. Tosi, D. Patel, C. Neuwirth, S. D. Horswell, A. D. Marais, C. van Heyningen, and A. K. Soutar.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.
17. Kwon, H. J., T. A. Lagace, M. C. McNutt, J. D. Horton, and J. Deisenhofer.2008.Molecular basis for LDL receptor recognition by PCSK9. Proc. Natl. Acad. Sci. USA.105 : 1820-1825.
18. Bottomley, M. J., A. Cirillo, L. Orsatti, L. Ruggeri, T. S. Fisher, J. C. Santoro, R. T. Cummings, R. M. Cubbon, P. Lo Surdo, A. Calzetta, et al.2009.Structural and biochemical characterization of the wild type PCSK9/EGF-AB complex and natural FH mutants. J. Biol. Chem. 284 : 1313-1323.
19. McNutt, M. C., H. J. Kwon, C. Chen, J. R. Chen, J. D. Horton, and T. A. Lagace.2009.Antagonism of secreted PCSK9 increases low-density lipoprotein receptor expression in HEPG2 cells. J. Biol. Chem. 284 : 10561-10570.
20. Cohen, J., A. Pertsemlidis, I. K. Kotowski, R. Graham, C. K. Garcia, and H. H. Hobbs.2005.Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat. Genet. 37 : 161-165.
21. Cohen, J. C., E. Boerwinkle, T. H. Mosley, and H. H. Hobbs.2006.Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354 : 1264-1272.
22. Stein, E. A., D. Gipe, J. Bergeron, D. Gaudet, R. Weiss, R. Dufour, R. Wu, and R. Pordy.2012.Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet.380 : 29-36.
23. Giugliano, R. P., N. R. Desai, P. Kohli, W. J. Rogers, R. Somaratne, F. Huang, T. Liu, S. Mohanavelu, E. B. Hoffman, S. T. McDonald, et al.2012.Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACETIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet.380 : 2007-2017.
24. Lee, P., and R. A. Hegele.2013.Current Phase II proprotein convertase subtilisin/kexin 9 inhibitor therapies for dyslipidemia. Expert Opin. Investig. Drugs.22 : 1411-1423.
25. Seidah, N. G., S. Benjannet, L. Wickham, J. Marcinkiewicz, S. B. Jasmin, S. Stifani, A. Basak, A. Prat, and M. Chretien.2003.The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. USA.100 : 928-933.
26. McNutt, M. C., T. A. Lagace, and J. D. Horton.2007.Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 Cells. J. Biol. Chem. 282 : 20799-20803.
27. Grefhorst, A., M. C. McNutt, T. A. Lagace, and J. D. Horton.2008.Plasma PCSK9 preferentially reduces liver LDL receptors in mice. J. Lipid Res. 49 : 1303-1311.
28. Zhang, D. W., R. Garuti, W. J. Tang, J. C. Cohen, and H. H. Hobbs.2008.Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc. Natl. Acad. Sci. USA.105 : 13045-13050.
29. Lo Surdo, P., M. J. Bottomley, A. Calzetta, E. C. Settembre, A. Cirillo, S. Pandit, Y. G. Ni, B. Hubbard, A. Sitlani, and A. Carfi.2011.Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. 12 : 1300-1305.
30. Tveten, K., T. B. Strom, K. E. Berge, and T. P. Leren.2013.PCSK9-mediated degradation of the LDL receptor generates a 17 kDa C-terminal LDL receptor fragment. J. Lipid Res. 54 : 1560-1566.
31. Yamamoto, T., C. Lu, and R. O. Ryan.2011.A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor. J. Biol. Chem. 286 : 5464-5470.
32. Du, F., Y. Hui, M. Zhang, M. F. Linton, S. Fazio, and D. Fan.2011.Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J. Biol. Chem. 286 : 43054-43061.
33. Saavedra, Y. G., R. Day, and N. G. Seidah.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.
34. Tveten, K., O. L. Holla, J. Cameron, T. B. Strom, K. E. Berge, J. K. Laerdahl, and T. P. Leren.2012.Interaction between the ligandbinding domain of the LDL receptor and the C-terminal domain of PCSK9 is required for PCSK9 to remain bound to the LDL receptor during endosomal acidification. Hum. Mol. Genet. 21 : 1402-1409.
35. Wang, Y., Y. Huang, H. H. Hobbs, and J. C. Cohen.2012.Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. J. Lipid Res. 53 : 1932-1943.
36. Russell, D. W., M. S. Brown, and J. L. Goldstein.1989.Different combinations of cysteine-rich repeats mediate binding of low density lipoprotein receptor to two different proteins. J. Biol. Chem. 264 : 21682-21688.
37. Brown, M. S., J. R. Faust, J. L. Goldstein, I. Kaneko, and A. Endo.978.Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase. J. Biol. Chem. 253 : 1121-1128.
38. Goldstein, J. L., S. K. Basu, and M. S. Brown.1983.Receptormediated endocytosis of low-density lipoprotein in cultured cells. Methods Enzymol. 98 : 241-260.
39. Kosenko, T., M. Golder, G. Leblond, W. Weng, and T. A. Lagace.2013.Low-density lipoprotein binds to proprotein convertase subtilisin/ kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated LDL receptor degradation. J. Biol. Chem. 288 : 8279-8288.
40. Lakoski, S. G., T. A. Lagace, J. C. Cohen, J. D. Horton, and H. H. Hobbs.2009.Genetic and metabolic determinants of plasma PCSK9 levels. J. Clin. Endocrinol. Metab. 94 : 2537-2543.
41. Beisiegel, U., W. J. Schneider, J. L. Goldstein, R. G. Anderson, and M. S. Brown.1981.Monoclonal antibodies to the low density lipoprotein receptor as probes for study of receptor-mediated endocytosis and the genetics of familial hypercholesterolemia. J. Biol. Chem. 256 : 11923-11931.
42. Cole, N. B., and J. G. Donaldson.2012.Releasable SNAP-tag probes for studying endocytosis and recycling. ACS Chem. Biol. 7 : 464-469.
43. Luo, Y., L. Warren, D. Xia, H. Jensen, T. Sand, S. Petras, W. Qin, K. S. Miller, and J. Hawkins.2009.Function and distribution of circulating human PCSK9 expressed extrahepatically in transgenic mice. J. Lipid Res. 50 : 1581-1588.
44. Seidah, N. G., S. Poirier, M. Denis, R. Parker, B. Miao, C. Mapelli, A. Prat, H. Wassef, J. Davignon, K. A. Hajjar, et al.2012.Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS ONE.7 : e41865.
45. Tavori, H., D. Fan, J. L. Blakemore, P. G. Yancey, L. Ding, M. F. Linton, and S. Fazio.2013.Serum proprotein convertase subtilisin/ kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation.127 : 2403-2413.
46. Mayer, G., S. Poirier, and N. G. Seidah.2008.Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J. Biol. Chem. 283 : 31791-31801.
47. DeVay, R. M., D. L. Shelton, and H. Liang.2013.Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2). J. Biol. Chem. 288 : 10805-10818.
48. Pathak, R. K., M. Yokode, R. E. Hammer, S. L. Hofmann, M. S. Brown, J. L. Goldstein, and R. G. Anderson.1990.Tissue-specific sorting of the human LDL receptor in polarized epithelia of transgenic mice. J. Cell Biol. 111 : 347-359.
49. Chaparro-Riggers, J., H. Liang, R. M. DeVay, L. Bai, J. E. Sutton, W. Chen, T. Geng, K. Lindquist, M. G. Casas, L. M. Boustany, et al. Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9. J. Biol. Chem. 287 : 11090-11097.
50. Davis, C. G., J. L. Goldstein, T. C. Sudhof, R. G. Anderson, D. W. Russell, and M. S. Brown.1987.Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature.326 : 760-765.
51. Hobbs, H. H., M. S. Brown, and J. L. Goldstein.1992.Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum. Mutat. 1 : 445-466.
52. van der Westhuyzen, D. R., M. L. Stein, H. E. Henderson, A. D. Marais, A. M. Fourie, and G. A. Coetzee.1991.Deletion of two growth-factor repeats from the low-density-lipoprotein receptor accelerates its degradation. Biochem. J. 277 : 677-682.
53. Maurer, M. E., and J. A. Cooper.2006.The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. J. Cell Sci. 119 : 4235-4246.
54. Jones, C., R. E. Hammer, W-P. Li, J. C. Cohen, H. H. Hobbs, and J. Herz.2003.Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia. J. Biol. Chem. 278 : 29024-29030.
55. Lakadamyali, M., M. J. Rust, and X. Zhuang.2006.Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes. Cell.124 : 997-1009.
56. Traub, L. M. 2009.Tickets to ride: selecting cargo for clathrin-regulated internalization. Nat. Rev. Mol. Cell Biol. 10 : 583-596.
57. Malby, S., R. Pickering, S. Saha, R. Smallridge, S. Linse, and A. K. Downing.2001.The first epidermal growth factor-like domain of the low-density lipoprotein receptor contains a noncanonical calcium binding site. Biochemistry.40 : 2555-2563.
58. Scott, C. C., and J. Gruenberg.2011.Ion flux and the function of endosomes and lysosomes: pH is just the start: the flux of ions across endosomal membranes influences endosome function not only through regulation of the luminal pH. Bioessays.33 : 103-110.
59. Diering, G. H., Y. Numata, S. Fan, J. Church, and M. Numata.2013. Endosomal Acidification by Na,+/H+ Exchanger NHE5 Regulates TrkA Cell-Surface Targeting and NGF-Induced PI3K Signaling. Mol. Biol. Cell.24 : 3435-3448.