PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain

Journal of Lipid Research

Volumn 51, Issue 9, 2010, Pages 2611-2618

  Liu, Mali ^a   Wu, Guoxin ^a   Baysarowich, Jennifer ^a   Kavana, Michael ^a   Addona, George H ^a   Bierilo, Kathleen K ^a   Mudgett, John S ^a   Pavlovic, Guillaume ^b   Sitlani, Ayesha ^a   Renger, John J ^a   Hubbard, Brian K ^a   Fisher, Timothy S ^a   Zerbinatti, Celina V ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b INSTITUT CLINIQUE DE LA SOURIS   (France)

Author keywords

site amyloid precursor protein cleaving enzyme 1; Alzheimer's disease; Amyloid ; Atherosclerosis; Low density lipoprotein; Proprotein convertase subtilisin kexin type 9

Indexed keywords

AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E2; BETA SECRETASE 1; LOW DENSITY LIPOPROTEIN RECEPTOR; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; SERINE PROTEINASE; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BRAIN; BRAIN CORTEX; CONTROLLED STUDY; EMBRYONIC STEM CELL; HIPPOCAMPUS; IN VITRO STUDY; IN VIVO STUDY; LIPID DEGRADATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LIPID INTERACTION; PROTEIN PROCESSING; PROTEIN TARGETING;

AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; BRAIN; HEK293 CELLS; HUMANS; LDL-RECEPTOR RELATED PROTEINS; MALE; MICE; MICE, KNOCKOUT; PROTEIN BINDING; RECEPTORS, LDL; SERINE ENDOPEPTIDASES;

EID: 77956844399     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M006635     Document Type: Article

References (42)

1. 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.
2. 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.
3. 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.
4. Abifadel, M., M. Varret, J. P. Rabès, 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.
5. Leren, T. P. 2004. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin. Genet. 65: 419-422.
6. Horton, J. D., J. C. Cohen, and H. H. Hobbs. 2007. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem. Sci. 32: 71-77.
7. Maxwell, K. N., and J. L. Breslow. 2004. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc. Natl. Acad. Sci. USA. 101: 7100-7105.
8. Rashid, S., D. E. Curtis, R. Garuti, N. N. Anderson, Y. Bashmakov, Y. K. Ho, R. E. Hammer, Y. A. Moon, and J. D. Horton. 2005. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc. Natl. Acad. Sci. USA. 102: 5374-5379.
9. 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.
10. Frank-Kamenetsky, M., A. Grefhorst, N. N. Anderson, T. S. Racie, B. Bramlage, A. Akinc, D. Butler, K. Charisse, R. Dorkin, Y. Fan, et al. 2008. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl. Acad. Sci. USA. 105: 11915-11920.
11. Graham, M. J., K. M. Lemonidis, C. P. Whipple, A. Subramaniam, B. P. Monia, S. T. Crooke, and R. M. Crooke. 2007. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J. Lipid Res. 48: 763-767.
12. Maxwell, K. N., E. A. Fisher, and J. L. Breslow. 2005. Overexpression of PCSK9 accelerates the degradation of the LDLR in a postendoplasmic reticulum compartment. Proc. Natl. Acad. Sci. USA. 102: 2069-2074.
13. 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.
14. 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.
15. 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 familial hypercholesterolemia mutants. J. Biol. Chem. 284: 1313-1323.
16. Shan, L., L. Pang, R. Zhang, N. J. Murgolo, H. Lan, and J. A. Hedrick. 2008. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem. Biophys. Res. Commun. 375: 69-73.
17. Duff, C. J., M. J. Scott, I. T. Kirby, S. E. Hutchinson, S. L. Martin, and N. M. Hooper. 2009. Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem. J. 419: 577-584.
18. Chan, J. C., D. E. Piper, Q. Cao, D. Liu, C. King, W. Wang, J. Tang, Q. Liu, J. Higbee, Z. Xia, et al. 2009. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc. Natl. Acad. Sci. USA. 106: 9820-9825.
19. 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.
20. Schmidt, R. J., T. P. Beyer, W. R. Bensch, Y. W. Qian, A. Lin, M. Kowala, W. E. Alborn, R. J. Konrad, and G. Cao. 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.
21. Poirier, S., G. Mayer, S. Benjannet, E. Bergeron, J. Marcinkiewicz, N. Nassoury, H. Mayer, J. Nimpf, A. Prat, and N. G. Seidah. 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.
22. Gåfvels, M. E., L. G. Paavola, C. O. Boyd, P. M. Nolan, F. Wittmaack, A. Chawla, M. A. Lazar, M. Bucan, B. O. Angelin, and J. F. Strauss 3rd. 1994. Cloning of a complementary deoxyribonucleic acid encoding the murine homolog of the very low density lipoprotein/apolipoprotein-E receptor: expression pattern and assignment of the gene to mouse chromosome 19. Endocrinology. 135: 387-394.
23. Kim, D. H., H. Iijima, K. Goto, J. Sakai, H. Ishii, H. J. Kim, H. Suzuki, H. Kondo, S. Saeki, and T. Yamamoto. 1996. Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. J. Biol. Chem. 271: 8373-8380.
24. Weeber, E. J., U. Beffert, C. Jones, J. M. Christian, E. Forster, J. D. Sweatt, and J. Herz. 2002. Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J. Biol. Chem. 277: 39944-39952.
25. Motoi, Y., M. Itaya, H. Mori, Y. Mizuno, T. Iwasaki, H. Hattori, S. Haga, and K. Ikeda. 2004. Apolipoprotein E receptor 2 is involved in neuritic plaque formation in APP sw mice. Neurosci. Lett. 368: 144-147.
26. Durakoglugil, M. S., Y. Chen, C. L. White, E. T. Kavalali, and J. Herz. 2009. Reelin signaling antagonizes beta-amyloid at the synapse. Proc. Natl. Acad. Sci. USA. 106: 15938-15943.
27. Vassar, R., B. D. Bennett, S. Babu-Khan, S. Kahn, E. A. Mendiaz, P. Denis, D. B. Teplow, S. Ross, P. Amarante, R. Loeloff, et al. 1999. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 286: 735-741.
28. Jonas, M. C., C. Costantini, and L. Puglielli. 2008. PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep. 9: 916-922.
29. Fisher, T. S., P. Lo Surdo, S. Pandit, M. Mattu, J. C. Santoro, D. Wisniewski, R. T. Cummings, A. Calzetta, R. M. Cubbon, P. A. Fischer, et al. 2007. Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation. J. Biol. Chem. 282: 20502-20512.
30. Pandit, S., D. Wisniewski, J. C. Santoro, S. Ha, V. Ramakrishnan, R. M. Cubbon, R. T. Cummings, S. D. Wright, C. P. Sparrow, A. Sitlani, et al. 2008. Functional analysis of sites within PCSK9 responsible for hypercholesterolemia. J. Lipid Res. 49: 1333-1343.
31. 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.
32. Abifadel, M., J. P. Rabès, 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.
33. Fryer, J. D., R. B. Demattos, L. M. McCormick, M. A. O'Dell, M. L. Spinner, K. R. Bale, S. M. Paul, P. M. Sullivan, M. Parsadanian, G. Bu, et al. 2005. The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice. J. Biol. Chem. 280: 25754-25759.
34. Liu, Q., C. V. Zerbinatti, J. Zhang, H. S. Hoe, B. Wang, S. L. Cole, J. Herz, L. Muglia, and G. Bu. 2007. Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron. 56: 66-78.
35. Strittmatter, W. J., A. M. Saunders, D. Schmechel, M. Pericak-Vance, J. Enghild, G. S. Salvesen, and A. D. Roses. 1993. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA. 90: 1977-1981.
36. Bu, G. 2009. Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nat. Rev. Neurosci. 10: 333-344.
37. Kim, J., J. M. Castellano, H. Jiang, J. M. Basak, M. Parsadanian, V. Pham, S. M. Mason, S. M. Paul, and D. M. Holtzman. 2009. Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance. Neuron. 64: 632-644.
38. Herz, J. 2009. Apolipoprotein E receptors in the nervous system. Curr. Opin. Lipidol. 20: 190-196.
39. Herz, J., and Y. Chen. 2006. Reelin, lipoprotein receptors and synaptic plasticity. Nat. Rev. Neurosci. 7: 850-859.
40. Chin, J., C. M. Massaro, J. J. Palop, M. T. Thwin, G. Q. Yu, N. Bien-Ly, A. Bender, and L. Mucke. 2007. Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's disease. J. Neurosci. 27: 2727-2733.
41. Park, S. W., Y. A. Moon, and J. D. Horton. 2004. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J. Biol. Chem. 279: 50630-50638.
42. Zelcer, N., C. Hong, R. Boyadjian, and P. Tontonoz. 2009. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 325: 100-104.