Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2)

Journal of Biological Chemistry

Volumn 288, Issue 15, 2013, Pages 10805-10818

  DeVay, Rachel M ^a   Shelton, David L ^a   Liang, Hong ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID PRECURSOR PROTEINS; ANTIBODY THERAPEUTICS; C-TERMINAL DOMAINS; LOW DENSITY LIPOPROTEIN RECEPTORS; PH-DEPENDENT; SOLUBLE PROTEINS; THERAPEUTIC ANTIBODIES; TRANS-MEMBRANE PROTEINS;

CATALYST ACTIVITY; GLYCOPROTEINS;

PROTEINS;

AMYLOID PRECURSOR LIKE PROTEIN 2; AMYLOID PRECURSOR PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; SUBTILISIN; UNCLASSIFIED DRUG;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL SELECTION; CONTROLLED STUDY; ENDOCYTOSIS; LYSOSOME; PH; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; PROTEIN TRANSPORT;

AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; ENDOCYTOSIS; HEP G2 CELLS; HUMANS; HYDROGEN-ION CONCENTRATION; LYSOSOMES; MICE; MODELS, BIOLOGICAL; NERVE TISSUE PROTEINS; PROPROTEIN CONVERTASES; PROTEIN TRANSPORT; PROTEOLYSIS; SERINE ENDOPEPTIDASES;

EID: 84876241355     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.453373     Document Type: Article

References (44)

1. Bonifacino, J. S., and Traub, L. M. (2003) Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu. Rev. Biochem. 72, 395-447
2. Tuli, A., Sharma, M., Capek, H. L., Naslavsky, N., Caplan, S., and Solheim, J. C. (2009) Mechanism for amyloid precursor-like protein 2 enhancement of major histocompatibility complex class I molecule degradation. J. Biol. Chem. 284, 34296-34307
3. Grant, B. D., and Donaldson, J. G. (2009) Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell Biol. 10, 597-608
4. Saftig, P., and Klumperman, J. (2009) Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat. Rev. 10, 623-635
5. Jeon, H., and Blacklow, S. C. (2005) Structure and physiologic function of the low-density lipoprotein receptor. Annu. Rev. Biochem. 74, 535-562
6. Beglova, N., Jeon, H., Fisher, C., and Blacklow, S. C. (2004) Structural features of the low-density lipoprotein receptor facilitating ligand binding and release. Biochem. Soc. Trans. 32, 721-723
7. 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
8. Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., and Hobbs, H. H. (2005) Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat. Genet. 37, 161-165
9. Maxwell, K. N., and Breslow, J. L. (2005) Proprotein convertase subtilisin kexin 9: the third locus implicated in autosomal dominant hypercholesterolemia. Curr. Opin. Lipidol. 16, 167-172
10. Tibolla, G., Norata, G. D., Artali, R., Meneghetti, F., and Catapano, A. L. (2011) Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure- function relation to therapeutic inhibition. Nutr. Metab. Cardiovasc. Dis. 21, 835-843
11. Strøm, T. B., Holla, O. 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
12. McNutt, M. C., Lagace, T. A., and Horton, J. D. (2007) Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J. Biol. Chem. 282, 20799-20803
13. 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
14. Zhang, D. W., Garuti, R., Tang, W. J., Cohen, J. C., and Hobbs, H. H. (2008) Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc. Natl. Acad. Sci. U.S.A. 105, 13045-13050
15. 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
16. 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
17. McNutt, M. C., Kwon, H. J., Chen, C., Chen, J. R., Horton, J. D., and Lagace, T. A. (2009) Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells. J. Biol. Chem. 284, 10561-10570
18. 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
19. Ni, Y. G., Condra, J. H., Orsatti, L., Shen, X., Di Marco, S., Pandit, S., Bottomley, M. J., Ruggeri, L., Cummings, R. T., Cubbon, R. M., Santoro, J. C., Ehrhardt, A., Lewis, D., Fisher, T. S., Ha, S., Njimoluh, L., Wood, D. D., Hammond, H. A., Wisniewski, D., Volpari, C., Noto, A., Lo Surdo, P., Hubbard, B., Carfí, A., and Sitlani, A. (2010) A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigenbinding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake. J. Biol. Chem. 285, 12882-12891
20. 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
21. Holla, O. L., Cameron, J., Tveten, K., Strom, T. B., Berge, K. E., Laerdahl, J. K., and Leren, T. P. (2011) Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors. J. Lipid Res. 52, 1787-1794
22. 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
23. 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
24. Liang, H., Chaparro-Riggers, J., Strop, P., Geng, T., Sutton, J. E., Tsai, D., Bai, L., Abdiche, Y., Dilley, J., Yu, J., Wu, S., Chin, S. M., Lee, N. A., Rossi, A., Lin, J. C., Rajpal, A., Pons, J., and Shelton, D. L. (2012) Proprotein convertase subtilisin/kexin type 9 antagonism reduces low-density lipoprotein cholesterol in statin-treated hypercholesterolemic nonhuman primates. J. Pharmacol. Exp. Ther. 340, 228-236
25. Chaparro-Riggers, J., Liang, H., DeVay, R. M., Bai, L., Sutton, J. E., Chen, W., Geng, T., Lindquist, K., Casas, M. G., Boustany, L. M., Brown, C. L., Chabot, J., Gomes, B., Garzone, P., Rossi, A., Strop, P., Shelton, D., Pons, J., and Rajpal, A. (2012) 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
26. Bustin, S. A., Benes, V., Garson, J. A., Hellemans, J., Huggett, J., Kubista, M., Mueller, R., Nolan, T., Pfaffl, M. W., Shipley, G. L., Vandesompele, J., and Wittwer, C. T. (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55, 611-622
27. Keller, A., Nesvizhskii, A. I., Kolker, E., and Aebersold, R. (2002) Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal. Chem. 74, 5383-5392
28. Nesvizhskii, A. I., Keller, A., Kolker, E., and Aebersold, R. (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646-4658
29. Jaskolski, F., Mulle, C., and Manzoni, O. J. (2005) An automated method to quantify and visualize colocalized fluorescent signals. J. Neurosci. Methods 146, 42-49
30. Ni, Y. G., Di Marco, S., Condra, J. H., Peterson, L. B., Wang, W., Wang, F., Pandit, S., Hammond, H. A., Rosa, R., Cummings, R. T., Wood, D. D., Liu, X., Bottomley, M. J., Shen, X., Cubbon, R. M., Wang, S. P., Johns, D. G., Volpari, C., Hamuro, L., Chin, J., Huang, L., Zhao, J. Z., Vitelli, S., Haytko, P., Wisniewski, D., Mitnaul, L. J., Sparrow, C. P., Hubbard, B., Carfí, A., and Sitlani, A. (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
31. Chan, J. C., Piper, D. E., Cao, Q., Liu, D., King, C., Wang, W., Tang, J., Liu, Q., Higbee, J., Xia, Z., Di, Y., Shetterly, S., Arimura, Z., Salomonis, H., Romanow, W. G., Thibault, S. T., Zhang, R., Cao, P., Yang, X. P., Yu, T., Lu, M., Retter, M. W., Kwon, G., Henne, K., Pan, O., Tsai, M. M., Fuchslocher, B., Yang, E., Zhou, L., Lee, K. J., Daris, M., Sheng, J., Wang, Y., Shen, W. D., Yeh, W. C., Emery, M., Walker, N. P., Shan, B., Schwarz, M., and Jackson, S. M. (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
32. Shan, L., Pang, L., Zhang, R., Murgolo, N. J., Lan, H., and Hedrick, J. A. (2008) PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem. Biophys. Res. Commun. 375, 69-73
33. 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
34. Goldstein, J. L., Anderson, R. G., and Brown, M. S. (1979) Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature 279, 679-685
35. Liu, M., Wu, G., Baysarowich, J., Kavana, M., Addona, G. H., Bierilo, K. K., Mudgett, J. S., Pavlovic, G., Sitlani, A., Renger, J. J., Hubbard, B. K., Fisher, T. S., and Zerbinatti, C. V. (2010) PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain. J. Lipid Res. 51, 2611-2618
36. Mettlen, M., Loerke, D., Yarar, D., Danuser, G., and Schmid, S. L. (2010) Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis. J. Cell Biol. 188, 919-933
37. Qian, Y. W., Schmidt, R. J., Zhang, Y., Chu, S., Lin, A., Wang, H., Wang, X., Beyer, T. P., Bensch, W. R., Li, W., Ehsani, M. E., Lu, D., Konrad, R. J., Eacho, P. I., Moller, D. E., Karathanasis, S. K., and Cao, G. (2007) Secreted PCSK9 downregulates low density lipoprotein receptor through receptormediated endocytosis. J. Lipid Res. 48, 1488-1498
38. 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
39. Wang, Y., Huang, Y., Hobbs, H. H., and Cohen, J. C. (2012) Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. J. Lipid Res. 53, 1932-1943
40. Holla, Ø. L., Strøm, T. B., Cameron, J., Berge, K. E., and Leren, T. P. (2010) A chimeric LDL receptor containing the cytoplasmic domain of the transferrin receptor is degraded by PCSK9. Mol. Genet. Metab. 99, 149-156
41. Tuli, A., Sharma, M., McIlhaney, M. M., Talmadge, J. E., Naslavsky, N., Caplan, S., and Solheim, J. C. (2008) Amyloid precursor-like protein 2 increases the endocytosis, instability, and turnover of the H2-K(d) MHC class I molecule. J. Immunol. 181, 1978-1987
42. Marzolo, M. P., and Bu, G. (2009) Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease. Semin. Cell Dev. Biol. 20, 191-200
43. Abisambra, J. F., Fiorelli, T., Padmanabhan, J., Neame, P., Wefes, I., and Potter, H. (2010) LDLR expression and localization are altered in mouse and human cell culture models of Alzheimer's disease. PLoS One 5, e8556
44. Jonas, M. C., Costantini, C., and Puglielli, L. (2008) PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep. 9, 916-922