Proteolytic processing of the prion protein in health and disease

American Journal of Neurodegenerative Diseases

Volumn 1, Issue 1, 2012, Pages 15-31

  Altmeppen, Hermann C ^a   Puig, Berta ^a   Dohler, Frank ^a   Thurm, Dana K ^a   Falker, Clemens ^a   Krasemann, Susanne ^a   Glatzel, Markus ^a  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

Author keywords

ADAM10; ADAM17; Ectodomain shedding; Prion protein; Proteolytic processing; cleavage; cleavage

Indexed keywords

ADAM PROTEIN; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE 1; PRION PROTEIN; PROTEIN KINASE C;

ANIMAL MODEL; HUMAN; MOUSE; NERVE DEGENERATION; NERVOUS SYSTEM; NEUROBLASTOMA CELL; NEUROTOXICITY; NONHUMAN; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; TRANSGENIC MOUSE;

EID: 84980052037     PISSN: None     EISSN: 2165591X     Source Type: Journal    
DOI: None     Document Type: Review

References (156)

1. Riek R, Hornemann S, Wider G, Glockshuber R and Wüthrich K. NMR characterization of the full-length recombinant murine prion protein, mPrP(23-231). FEBS Lett 1997; 413: 282-288.
2. Biasini E, Turnbaugh JA, Unterberger U and Harris DA. Prion protein at the crossroads of physiology and disease. Trends Neurosci 2012; 35: 92-103.
3. Brugger B, Graham C, Leibrecht I, Mombelli E, Jen A, Wieland F and Morris R. The membrane domains occupied by glycosylphosphatidylinosi tol-anchored prion protein and Thy-1 differ in lipid composition. J Biol Chem 2004; 279: 7530-7536.
4. Taylor DR and Hooper NM. The prion protein and lipid rafts. Mol Membr Biol 2006; 23: 89-99.
5. Linden R, Martins VR, Prado MA, Cammarota M, Izquierdo I and Brentani RR. Physiology of the prion protein. Physiol Rev 2008; 88: 673-728.
6. Aguzzi A and Polymenidou M. Mammalian prion biology: one century of evolving concepts. Cell 2004; 116: 313-327.
7. Aguzzi A, Baumann F and Bremer J. The prion's elusive reason for being. Annu Rev Neurosci 2008; 31: 439-477.
8. Graner E, Mercadante AF, Zanata SM, Forlenza OV, Cabral AL, Veiga SS, Juliano MA, Roesler R, Walz R, Minetti A, Izquierdo I, Martins VR and Brentani RR. Cellular prion protein binds laminin and mediates neuritogenesis. Brain Res Mol Brain Res 2000; 76: 85-92.
9. Steele AD, Emsley JG, Ozdinler PH, Lindquist S and Macklis JD. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proc Natl Acad Sci U S A 2006; 103: 3416-3421.
10. Hajj GN, Lopes MH, Mercadante AF, Veiga SS, da Silveira RB, Santos TG, Ribeiro KC, Juliano MA, Jacchieri SG, Zanata SM and Martins VR. Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins. J Cell Sci 2007; 120: 1915-1926.
11. Mange A, Milhavet O, Umlauf D, Harris D and Lehmann S. PrP-dependent cell adhesion in N2a neuroblastoma cells. FEBS Lett 2002; 514: 159-162.
12. Malaga-Trillo E, Solis GP, Schrock Y, Geiss C, Luncz L, Thomanetz V and Stuermer CA. Regulation of embryonic cell adhesion by the prion protein. PLoS Biol 2009; 7: e55.
13. Chiarini LB, Freitas AR, Zanata SM, Brentani RR, Martins VR and Linden R. Cellular prion protein transduces neuroprotective signals. EMBO J 2002; 21: 3317-3326.
14. Rambold AS, Muller V, Ron U, Ben-Tal N, Winklhofer KF and Tatzelt J. Stress-protective signalling of prion protein is corrupted by scrapie prions. EMBO J 2008; 27: 1974-1984.
15. Brown DR. Prion protein expression modulates neuronal copper content. J Neurochem 2003; 87: 377-385.
16. Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM and Kellermann O. Signal transduction through prion protein. Science 2000; 289: 1925-1928.
17. Mouillet-Richard S, Schneider B, Pradines E, Pietri M, Ermonval M, Grassi J, Richards JG, Mutel V, Launay JM and Kellermann O. Cellular prion protein signaling in serotonergic neuronal cells. Ann N Y Acad Sci 2007; 1096: 106-119.
18. Solforosi L, Criado JR, McGavern DB, Wirz S, Sanchez-Alavez M, Sugama S, DeGiorgio LA, Volpe BT, Wiseman E, Abalos G, Masliah E, Gilden D, Oldstone MB, Conti B and Williamson RA. Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science 2004; 303: 1514-1516.
19. Resenberger UK, Harmeier A, Woerner AC, Goodman JL, Muller V, Krishnan R, Vabulas RM, Kretzschmar HA, Lindquist S, Hartl FU, Multhaup G, Winklhofer KF and Tatzelt J. The cellular prion protein mediates neurotoxic signalling of beta-sheet-rich conformers independent of prion replication. EMBO J 2011; 30: 2057-2070.
20. You H, Tsutsui S, Hameed S, Kannanayakal TJ, Chen L, Xia P, Engbers JD, Lipton SA, Stys PK and Zamponi GW. Abeta neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors. Proc Natl Acad Sci U S A 2012; 109: 1737-1742.
21. Prusiner SB. The prion diseases. Brain Pathol 1998; 8: 499-513.
22. Imran M and Mahmood S. An overview of human prion diseases. Virol J 2011; 8: 559.
23. Imran M and Mahmood S. An overview of animal prion diseases. Virol J 2011; 8: 493.
24. Prusiner SB. Prions. Proc Natl Acad Sci U S A 1998; 95: 13363-13383.
25. Sandberg MK, Al-Doujaily H, Sharps B, Clarke AR and Collinge J. Prion propagation and toxicity in vivo occur in two distinct mechanistic phases. Nature 2011; 470: 540-542.
26. Aguzzi A and Calella AM. Prions: protein aggregation and infectious diseases. Physiol Rev 2009; 89: 1105-1152.
27. Bueler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M and Weissmann C. Mice devoid of PrP are resistant to scrapie. Cell 1993; 73: 1339-1347.
28. Brandner S, Isenmann S, Raeber A, Fischer M, Sailer A, Kobayashi Y, Marino S, Weissmann C and Aguzzi A. Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 1996; 379: 339-343.
29. Lauren J, Gimbel DA, Nygaard HB, Gilbert JW and Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 2009; 457: 1128-1132.
30. Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Lauren J, Gimbel ZA and Strittmatter SM. Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neurosci 2010; 30: 6367-6374.
31. Balducci C, Beeg M, Stravalaci M, Bastone A, Sclip A, Biasini E, Tapella L, Colombo L, Manzoni C, Borsello T, Chiesa R, Gobbi M, Salmona M and Forloni G. Synthetic amyloid-beta oligomers impair long-term memory independ ently of cellular prion protein. Proc Natl Acad Sci U S A 2010; 107: 2295-2300.
32. Calella AM, Farinelli M, Nuvolone M, Mirante O, Moos R, Falsig J, Mansuy IM and Aguzzi A. Prion protein and Abeta-related synaptic toxicity impairment. EMBO Mol Med 2010; 2: 306-314.
33. Kessels HW, Nguyen LN, Nabavi S and Malinow R. The prion protein as a receptor for amyloidbeta. Nature 2010; 466: E3-4; discussion E4-5.
34. Parkin ET, Watt NT, Hussain I, Eckman EA, Eckman CB, Manson JC, Baybutt HN, Turner AJ and Hooper NM. Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein. Proc Natl Acad Sci U S A 2007; 104: 11062-11067.
35. Griffiths HH, Whitehouse IJ, Baybutt H, Brown D, Kellett KA, Jackson CD, Turner AJ, Piccardo P, Manson JC and Hooper NM. Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein. J Biol Chem 2011; 286: 33489-33500.
36. Notari S, Capellari S, Giese A, Westner I, Baruzzi A, Ghetti B, Gambetti P, Kretzschmar HA and Parchi P. Effects of different experimental conditions on the PrPSc core generated by protease digestion: implications for strain typing and molecular classification of CJD. J Biol Chem 2004; 279: 16797-16804.
37. Owen JP, Maddison BC, Whitelam GC and Gough KC. Use of thermolysin in the diagnosis of prion diseases. Mol Biotechnol 2007; 35: 161-170.
38. Cronier S, Gros N, Tattum MH, Jackson GS, Clarke AR, Collinge J and Wadsworth JD. Detection and characterization of proteinase Ksensitive disease-related prion protein with thermolysin. Biochem J 2008; 416: 297-305.
39. Nicot S and Baron TG. Strain-specific proteolytic processing of the prion protein in prion diseases of ruminants transmitted in ovine transgenic mice. J Gen Virol 2010; 91: 570-574.
40. Bremer J, Baumann F, Tiberi C, Wessig C, Fischer H, Schwarz P, Steele AD, Toyka KV, Nave KA, Weis J and Aguzzi A. Axonal prion protein is required for peripheral myelin maintenance. Nat Neurosci 2010; 13: 310-318.
41. Altmeppen HC, Prox J, Puig B, Kluth MA, Bernreuther C, Thurm D, Jorissen E, Petrowitz B, Bartsch U, De Strooper B, Saftig P and Glatzel M. Lack of a-disintegrin-and-metalloproteinase ADAM10 leads to intracellular accumulation and loss of shedding of the cellular prion protein in vivo. Mol Neurodegener 2011; 6: 36.
42. Harris DA, Huber MT, van Dijken P, Shyng SL, Chait BT and Wang R. Processing of a cellular prion protein: identification of N-and C-terminal cleavage sites. Biochemistry 1993; 32: 1009-1016.
43. Shyng SL, Huber MT and Harris DA. A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. J Biol Chem 1993; 268: 15922-15928.
44. Chen SG, Teplow DB, Parchi P, Teller JK, Gambetti P and Autilio-Gambetti L. Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem 1995; 270: 19173-19180.
45. Mange A, Beranger F, Peoc'h K, Onodera T, Frobert Y and Lehmann S. Alpha-and betacleavages of the amino-terminus of the cellular prion protein. Biol Cell 2004; 96: 125-132.
46. Vincent B, Paitel E, Frobert Y, Lehmann S, Grassi J and Checler F. Phorbol ester-regulated cleavage of normal prion protein in HEK293 human cells and murine neurons. J Biol Chem 2000; 275: 35612-35616.
47. Westergard L, Turnbaugh JA and Harris DA. A naturally occurring C-terminal fragment of the prion protein (PrP) delays disease and acts as a dominant-negative inhibitor of PrPSc formation. J Biol Chem 2011; 286: 44234-44242.
48. Taraboulos A, Scott M, Semenov A, Avrahami D, Laszlo L and Prusiner SB. Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform. J Cell Biol 1995; 129: 121-132.
49. Walmsley AR, Watt NT, Taylor DR, Perera WS and Hooper NM. alpha-cleavage of the prion protein occurs in a late compartment of the secretory pathway and is independent of lipid rafts. Mol Cell Neurosci 2009; 40: 242-248.
50. Zhao H, Klingeborn M, Simonsson M and Linne T. Proteolytic cleavage and shedding of the bovine prion protein in two cell culture systems. Virus Res 2006; 115: 43-55.
51. Barnewitz K, Maringer M, Mitteregger G, Giese A, Bertsch U and Kretzschmar HA. Unaltered prion protein cleavage in plasminogen-deficient mice. Neuroreport 2006; 17: 527-530.
52. Hachiya N, Komata Y, Harguem S, Nishijima K and Kaneko K. Possible involvement of calpainlike activity in normal processing of cellular prion protein. Neurosci Lett 2011; 490: 150-155.
53. Reiss K and Saftig P. The "a disintegrin and metalloprotease" (ADAM) family of sheddases: physiological and cellular functions. Semin Cell Dev Biol 2009; 20: 126-137.
54. Klein T and Bischoff R. Active metalloproteases of the A Disintegrin and Metalloprotease (ADAM) family: biological function and structure. J Proteome Res 2011; 10: 17-33.
55. Vincent B, Paitel E, Saftig P, Frobert Y, Hartmann D, De Strooper B, Grassi J, Lopez-Perez E and Checler F. The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein. J Biol Chem 2001; 276: 37743-37746.
56. Cisse MA, Sunyach C, Lefranc-Jullien S, Postina R, Vincent B and Checler F. The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. J Biol Chem 2005; 280: 40624-40631.
57. Heiseke A, Schobel S, Lichtenthaler SF, Vorberg I, Groschup MH, Kretzschmar H, Schatzl HM and Nunziante M. The novel sorting nexin SNX33 interferes with cellular PrP formation by modulation of PrP shedding. Traffic 2008; 9: 1116-1129.
58. Jimenez-Huete A, Lievens PM, Vidal R, Piccardo P, Ghetti B, Tagliavini F, Frangione B and Prelli F. Endogenous proteolytic cleavage of normal and disease-associated isoforms of the human prion protein in neural and non-neural tissues. Am J Pathol 1998; 153: 1561-1572.
59. Laffont-Proust I, Faucheux BA, Hassig R, Sazdovitch V, Simon S, Grassi J, Hauw JJ, Moya KL and Haik S. The N-terminal cleavage of cellular prion protein in the human brain. FEBS Lett 2005; 579: 6333-6337.
60. Taylor DR, Parkin ET, Cocklin SL, Ault JR, Ashcroft AE, Turner AJ and Hooper NM. Role of ADAMs in the ectodomain shedding and conformational conversion of the prion protein. J Biol Chem 2009; 284: 22590-22600.
61. Endres K, Mitteregger G, Kojro E, Kretzschmar H and Fahrenholz F. Influence of ADAM10 on prion protein processing and scrapie infectiosity in vivo. Neurobiol Dis 2009; 36: 233-241.
62. Liang J, Wang W, Sorensen D, Medina S, Ilchenko S, Kiselar J, Surewicz WK, Booth SA and Kong Q. Cellular prion protein regulates its own alpha-cleavage through ADAM8 in skeletal muscle. J Biol Chem 2012
63. Checler F. Two-steps control of cellular prion physiology by the Extracellular Regulated Kinase-1 (ERK1). Prion 2012; 6: 23-25.
64. Alfa Cisse M, Sunyach C, Slack BE, Fisher A, Vincent B and Checler F. M1 and M3 muscarinic receptors control physiological processing of cellular prion by modulating ADAM17 phosphorylation and activity. J Neurosci 2007; 27: 4083-4092.
65. Alfa Cisse M, Louis K, Braun U, Mari B, Leitges M, Slack BE, Fisher A, Auberger P, Checler F and Vincent B. Isoform-specific contribution of protein kinase C to prion processing. Mol Cell Neurosci 2008; 39: 400-410.
66. Cisse M, Duplan E, Guillot-Sestier MV, Rumigny J, Bauer C, Pages G, Orzechowski HD, Slack BE, Checler F and Vincent B. The extracellular regulated kinase-1 (ERK1) controls regulated alphasecretase-mediated processing, promoter transactivation, and mRNA levels of the cellular prion protein. J Biol Chem 2011; 286: 29192-29206.
67. Vincent B, Sunyach C, Orzechowski HD, St George-Hyslop P and Checler F. p53-Dependent transcriptional control of cellular prion by presenilins. J Neurosci 2009; 29: 6752-6760.
68. Lewis V, Whitehouse IJ, Baybutt H, Manson JC, Collins SJ and Hooper NM. Cellular prion protein expression is not regulated by the Alzheimer's amyloid precursor protein intracellular domain. PLoS One 2012; 7: e31754.
69. Haigh CL, Lewis VA, Vella LJ, Masters CL, Hill AF, Lawson VA and Collins SJ. PrPC-related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site. Cell Res 2009; 19: 1062-1078.
70. Oliveira-Martins JB, Yusa S, Calella AM, Bridel C, Baumann F, Dametto P and Aguzzi A. Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations. PLoS One 2010; 5: e9107.
71. Lutz J, Brabeck C, Niemann HH, Kloz U, Korth C, Lingappa VR and Burkle A. Microdeletions within the hydrophobic core region of cellular prion protein alter its topology and metabolism. Biochem Biophys Res Commun 2010; 393: 439-444.
72. Mohan MJ, Seaton T, Mitchell J, Howe A, Blackburn K, Burkhart W, Moyer M, Patel I, Waitt GM, Becherer JD, Moss ML and Milla ME. The tumor necrosis factor-alpha converting enzyme (TACE): a unique metalloproteinase with highly defined substrate selectivity. Biochemistry 2002; 41: 9462-9469.
73. Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C and Fahrenholz F. Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci U S A 1999; 96: 3922-3927.
74. Jorissen E, Prox J, Bernreuther C, Weber S, Schwanbeck R, Serneels L, Snellinx A, Craessaerts K, Thathiah A, Tesseur I, Bartsch U, Weskamp G, Blobel CP, Glatzel M, De Strooper B and Saftig P. The disintegrin/ metalloproteinase ADAM10 is essential for the establishment of the brain cortex. J Neurosci 2010; 30: 4833-4844.
75. Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Rossner S and Lichtenthaler SF. ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J 2010; 29: 3020-3032.
76. Epis R, Marcello E, Gardoni F, Vastagh C, Malinverno M, Balducci C, Colombo A, Borroni B, Vara H, Dell'Agli M, Cattabeni F, Giustetto M, Borsello T, Forloni G, Padovani A and Di Luca M. Blocking ADAM10 synaptic trafficking generates a model of sporadic Alzheimer's disease. Brain 2010; 133: 3323-3335.
77. Beland M and Roucou X. The prion protein unstructured N-terminal region is a broadspectrum molecular sensor with diverse and contrasting potential functions. J Neurochem 2012; 120: 853-868.
78. Guillot-Sestier MV, Sunyach C, Druon C, Scarzello S and Checler F. The alpha-secretasederived N-terminal product of cellular prion, N1, displays neuroprotective function in vitro and in vivo. J Biol Chem 2009; 284: 35973-35986.
79. Chen S, Yadav SP and Surewicz WK. Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues. J Biol Chem 2010; 285: 26377-26383.
80. Guillot-Sestier MV, Sunyach C, Ferreira ST, Marzolo MP, Bauer C, Thevenet A and Checler F. alpha-Secretase-derived fragment of cellular prion, N1, protects against monomeric and oligomeric amyloid beta (Abeta)-associated cell death. J Biol Chem 2012; 287: 5021-5032.
81. Resenberger UK, Winklhofer KF and Tatzelt J. Cellular Prion Protein Mediates Toxic Signaling of Amyloid Beta. Neurodegener Dis 2011
82. Mallucci G, Dickinson A, Linehan J, Klohn PC, Brandner S and Collinge J. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 2003; 302: 871-874.
83. Chung E, Ji Y, Sun Y, Kascsak RJ, Kascsak RB, Mehta PD, Strittmatter SM and Wisniewski T. Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an Alzheimer's disease model mouse. BMC Neurosci 2010; 11: 130.
84. Shmerling D, Hegyi I, Fischer M, Blattler T, Brandner S, Gotz J, Rulicke T, Flechsig E, Cozzio A, von Mering C, Hangartner C, Aguzzi A and Weissmann C. Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 1998; 93: 203-214.
85. Li A, Barmada SJ, Roth KA and Harris DA. Nterminally deleted forms of the prion protein activate both Bax-dependent and Baxindependent neurotoxic pathways. J Neurosci 2007; 27: 852-859.
86. Paitel E, Fahraeus R and Checler F. Cellular prion protein sensitizes neurons to apoptotic stimuli through Mdm2-regulated and p53-dependent caspase 3-like activation. J Biol Chem 2003; 278: 10061-10066.
87. Paitel E, Sunyach C, Alves da Costa C, Bourdon JC, Vincent B and Checler F. Primary cultured neurons devoid of cellular prion display lower responsiveness to staurosporine through the control of p53 at both transcriptional and posttranscriptional levels. J Biol Chem 2004; 279: 612-618.
88. Sunyach C, Cisse MA, da Costa CA, Vincent B and Checler F. The C-terminal products of cellular prion protein processing, C1 and C2, exert distinct influence on p53-dependent staurosporine-induced caspase-3 activation. J Biol Chem 2007; 282: 1956-1963.
89. Sunyach C and Checler F. Combined pharmacological, mutational and cell biology approaches indicate that p53-dependent caspase 3 activation triggered by cellular prion is dependent on its endocytosis. J Neurochem 2005; 92: 1399-1407.
90. Radovanovic I, Braun N, Giger OT, Mertz K, Miele G, Prinz M, Navarro B and Aguzzi A. Truncated prion protein and Doppel are myelinotoxic in the absence of oligodendrocytic PrPC. J Neurosci 2005; 25: 4879-4888.
91. Nishida N, Tremblay P, Sugimoto T, Shigematsu K, Shirabe S, Petromilli C, Erpel SP, Nakaoke R, Atarashi R, Houtani T, Torchia M, Sakaguchi S, DeArmond SJ, Prusiner SB and Katamine S. A mouse prion protein transgene rescues mice deficient for the prion protein gene from purkinje cell degeneration and demyelination. Lab Invest 1999; 79: 689-697.
92. Pauly PC and Harris DA. Copper stimulates endocytosis of the prion protein. J Biol Chem 1998; 273: 33107-33110.
93. Perera WS and Hooper NM. Ablation of the metal ion-induced endocytosis of the prion protein by disease-associated mutation of the octarepeat region. Curr Biol 2001; 11: 519-523.
94. Haigh CL, Edwards K and Brown DR. Copper binding is the governing determinant of prion protein turnover. Mol Cell Neurosci 2005; 30: 186-196.
95. Nunziante M, Gilch S and Schatzl HM. Essential role of the prion protein N terminus in subcellular trafficking and half-life of cellular prion protein. J Biol Chem 2003; 278: 3726-3734.
96. Sunyach C, Jen A, Deng J, Fitzgerald KT, Frobert Y, Grassi J, McCaffrey MW and Morris R. The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein. EMBO J 2003; 22: 3591-3601.
97. Taylor DR, Watt NT, Perera WS and Hooper NM. Assigning functions to distinct regions of the Nterminus of the prion protein that are involved in its copper-stimulated, clathrin-dependent endocytosis. J Cell Sci 2005; 118: 5141-5153.
98. Taylor DR and Hooper NM. The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion protein. Biochem J 2007; 402: 17-23.
99. Parkyn CJ, Vermeulen EG, Mootoosamy RC, Sunyach C, Jacobsen C, Oxvig C, Moestrup S, Liu Q, Bu G, Jen A and Morris RJ. LRP1 controls biosynthetic and endocytic trafficking of neuronal prion protein. J Cell Sci 2008; 121: 773-783.
100. Turnbaugh JA, Westergard L, Unterberger U, Biasini E and Harris DA. The N-terminal, polybasic region is critical for prion protein neuroprotective activity. PLoS One 2011; 6: e25675.
101. Diederich S and Maisner A. Molecular characteristics of the Nipah virus glycoproteins. Ann N Y Acad Sci 2007; 1102: 39-50.
102. Diederich S, Sauerhering L, Weis M, Altmeppen H, Schaschke N, Reinheckel T, Erbar S and Maisner A. Activation of the Nipah virus fusion protein in MDCK cells is mediated by cathepsin B within the endosome-recycling compartment. J Virol 2012; 86: 3736-3745.
103. Gasset M, Baldwin MA, Lloyd DH, Gabriel JM, Holtzman DM, Cohen F, Fletterick R and Prusiner SB. Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid. Proc Natl Acad Sci U S A 1992; 89: 10940-10944.
104. Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O and Tagliavini F. Neurotoxicity of a prion protein fragment. Nature 1993; 362: 543-546.
105. Tagliavini F, Prelli F, Verga L, Giaccone G, Sarma R, Gorevic P, Ghetti B, Passerini F, Ghibaudi E, Forloni G and et al. Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro. Proc Natl Acad Sci U S A 1993; 90: 9678-9682.
106. Stohr J, Watts JC, Legname G, Oehler A, Lemus A, Nguyen HO, Sussman J, Wille H, DeArmond SJ, Prusiner SB and Giles K. Spontaneous generation of anchorless prions in transgenic mice. Proc Natl Acad Sci U S A 2011; 108: 21223-21228.
107. Norstrom EM and Mastrianni JA. The AGAAAAGA palindrome in PrP is required to generate a productive PrPSc-PrPC complex that leads to prion propagation. J Biol Chem 2005; 280: 27236-27243.
108. Lewis V, Hill AF, Haigh CL, Klug GM, Masters CL, Lawson VA and Collins SJ. Increased proportions of C1 truncated prion protein protect against cellular M1000 prion infection. J Neuropathol Exp Neurol 2009; 68: 1125-1135.
109. Caughey B, Raymond GJ, Ernst D and Race RE. N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state. J Virol 1991; 65: 6597-6603.
110. Bolton DC, Bendheim PE, Marmorstein AD and Potempska A. Isolation and structural studies of the intact scrapie agent protein. Arch Biochem Biophys 1987; 258: 579-590.
111. Stahl N, Baldwin MA, Teplow DB, Hood L, Gibson BW, Burlingame AL and Prusiner SB. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry 1993; 32: 1991-2002.
112. Oesch B, Westaway D, Walchli M, McKinley MP, Kent SB, Aebersold R, Barry RA, Tempst P, Teplow DB, Hood LE and et al. A cellular gene encodes scrapie PrP 27-30 protein. Cell 1985; 40: 735-746.
113. Yadavalli R, Guttmann RP, Seward T, Centers AP, Williamson RA and Telling GC. Calpaindependent endoproteolytic cleavage of PrPSc modulates scrapie prion propagation. J Biol Chem 2004; 279: 21948-21956.
114. McMahon HE, Mange A, Nishida N, Creminon C, Casanova D and Lehmann S. Cleavage of the amino terminus of the prion protein by reactive oxygen species. J Biol Chem 2001; 276: 2286-2291.
115. Milhavet O and Lehmann S. Oxidative stress and the prion protein in transmissible spongiform encephalopathies. Brain Res Brain Res Rev 2002; 38: 328-339.
116. Lee DW, Sohn HO, Lim HB, Lee YG, Kim YS, Carp RI and Wisniewski HM. Alteration of free radical metabolism in the brain of mice infected with scrapie agent. Free Radic Res 1999; 30: 499-507.
117. Guentchev M, Voigtlander T, Haberler C, Groschup MH and Budka H. Evidence for oxidative stress in experimental prion disease. Neurobiol Dis 2000; 7: 270-273.
118. Choi SI, Ju WK, Choi EK, Kim J, Lea HZ, Carp RI, Wisniewski HM and Kim YS. Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent. Acta Neuropathol 1998; 96: 279-286.
119. Milhavet O, McMahon HE, Rachidi W, Nishida N, Katamine S, Mange A, Arlotto M, Casanova D, Riondel J, Favier A and Lehmann S. Prion infection impairs the cellular response to oxidative stress. Proc Natl Acad Sci U S A 2000; 97: 13937-13942.
120. Watt NT, Taylor DR, Gillott A, Thomas DA, Perera WS and Hooper NM. Reactive oxygen species-mediated beta-cleavage of the prion protein in the cellular response to oxidative stress. J Biol Chem 2005; 280: 35914-35921.
121. Pushie MJ and Vogel HJ. Modeling by assembly and molecular dynamics simulations of the low Cu2+ occupancy form of the mammalian prion protein octarepeat region: gaining insight into Cu2+-mediated beta-cleavage. Biophys J 2008; 95: 5084-5091.
122. Borchelt DR, Rogers M, Stahl N, Telling G and Prusiner SB. Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor. Glycobiology 1993; 3: 319-329.
123. Stahl N, Borchelt DR, Hsiao K and Prusiner SB. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 1987; 51: 229-240.
124. Parizek P, Roeckl C, Weber J, Flechsig E, Aguzzi A and Raeber AJ. Similar turnover and shedding of the cellular prion protein in primary lymphoid and neuronal cells. J Biol Chem 2001; 276: 44627-44632.
125. Tagliavini F, Prelli F, Porro M, Salmona M, Bugiani O and Frangione B. A soluble form of prion protein in human cerebrospinal fluid: implications for prion-related encephalopathies. Biochem Biophys Res Commun 1992; 184: 1398-1404.
126. Perini F, Vidal R, Ghetti B, Tagliavini F, Frangione B and Prelli F. PrP27-30 is a normal soluble prion protein fragment released by human platelets. Biochem Biophys Res Commun 1996; 223: 572-577.
127. MacGregor I, Hope J, Barnard G, Kirby L, Drummond O, Pepper D, Hornsey V, Barclay R, Bessos H, Turner M and Prowse C. Application of a time-resolved fluoroimmunoassay for the analysis of normal prion protein in human blood and its components. Vox Sang 1999; 77: 88-96.
128. Li R, Liu T, Yoshihiro F, Tary-Lehmann M, Obrenovich M, Kuekrek H, Kang SC, Pan T, Wong BS, Medof ME and Sy MS. On the same cell type GPI-anchored normal cellular prion and DAF protein exhibit different biological properties. Biochem Biophys Res Commun 2003; 303: 446-451.
129. Parkin ET, Watt NT, Turner AJ and Hooper NM. Dual mechanisms for shedding of the cellular prion protein. J Biol Chem 2004; 279: 11170-11178.
130. Stahl N, Baldwin MA, Burlingame AL and Prusiner SB. Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein. Biochemistry 1990; 29: 8879-8884.
131. Tousseyn T, Thathiah A, Jorissen E, Raemaekers T, Konietzko U, Reiss K, Maes E, Snellinx A, Serneels L, Nyabi O, Annaert W, Saftig P, Hartmann D and De Strooper B. ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. J Biol Chem 2009; 284: 11738-11747.
132. Moss ML, Powell G, Miller MA, Edwards L, Qi B, Sang QX, De Strooper B, Tesseur I, Lichtenthaler SF, Taverna M, Zhong JL, Dingwall C, Ferdous T, Schlomann U, Zhou P, Griffith LG, Lauffenburger DA, Petrovich R and Bartsch JW. ADAM9 inhibition increases membrane activity of ADAM10 and controls alpha-secretase processing of amyloid precursor protein. J Biol Chem 2011; 286: 40443-40451.
133. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M and Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123: 291-304.
134. Janes PW, Wimmer-Kleikamp SH, Frangakis AS, Treble K, Griesshaber B, Sabet O, Grabenbauer M, Ting AY, Saftig P, Bastiaens PI and Lackmann M. Cytoplasmic relaxation of active Eph controls ephrin shedding by ADAM10. PLoS Biol 2009; 7: e1000215.
135. Weskamp G, Ford JW, Sturgill J, Martin S, Docherty AJ, Swendeman S, Broadway N, Hartmann D, Saftig P, Umland S, Sehara-Fujisawa A, Black RA, Ludwig A, Becherer JD, Conrad DH and Blobel CP. ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23. Nat Immunol 2006; 7: 1293-1298.
136. Mathews JA, Gibb DR, Chen BH, Scherle P and Conrad DH. CD23 Sheddase A disintegrin and metalloproteinase 10 (ADAM10) is also required for CD23 sorting into B cell-derived exosomes. J Biol Chem 2010; 285: 37531-37541.
137. Donmez G, Wang D, Cohen DE and Guarente L. SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell 2010; 142: 320-332.
138. Prox J, Willenbrock M, Weber S, Lehmann T, Schmidt-Arras D, Schwanbeck R, Saftig P and Schwake M. Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cell Mol Life Sci 2012
139. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST and Klein WL. Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptordependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 2007; 282: 11590-11601.
140. Khosravani H, Zhang Y, Tsutsui S, Hameed S, Altier C, Hamid J, Chen L, Villemaire M, Ali Z, Jirik FR and Zamponi GW. Prion protein attenuates excitotoxicity by inhibiting NMDA receptors. J Cell Biol 2008; 181: 551-565.
141. Caetano FA, Beraldo FH, Hajj GN, Guimaraes AL, Jurgensen S, Wasilewska-Sampaio AP, Hirata PH, Souza I, Machado CF, Wong DY, De Felice FG, Ferreira ST, Prado VF, Rylett RJ, Martins VR and Prado MA. Amyloid-beta oligomers increase the localization of prion protein at the cell surface. J Neurochem 2011; 117: 538-553.
142. Wan XZ, Li B, Li YC, Yang XL, Zhang W, Zhong L and Tang SJ. Activation of NMDA Receptors Upregulates A Disintegrin and Metalloproteinase 10 via a Wnt/MAPK Signaling Pathway. J Neurosci 2012; 32: 3910-3916.
143. Marella M, Lehmann S, Grassi J and Chabry J. Filipin prevents pathological prion protein accumulation by reducing endocytosis and inducing cellular PrP release. J Biol Chem 2002; 277: 25457-25464.
144. Caughey B and Raymond GJ. The scrapieassociated form of PrP is made from a cell surface precursor that is both protease-and phospholipase-sensitive. J Biol Chem 1991; 266: 18217-18223.
145. Borchelt DR, Taraboulos A and Prusiner SB. Evidence for synthesis of scrapie prion proteins in the endocytic pathway. J Biol Chem 1992; 267: 16188-16199.
146. Enari M, Flechsig E and Weissmann C. Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc Natl Acad Sci U S A 2001; 98: 9295-9299.
147. Lewis PA, Properzi F, Prodromidou K, Clarke AR, Collinge J and Jackson GS. Removal of the glycosylphosphatidylinositol anchor from PrP(Sc) by cathepsin D does not reduce prion infectivity. Biochem J 2006; 395: 443-448.
148. Stahl N, Borchelt DR and Prusiner SB. Differential release of cellular and scrapie prion pro teins from cellular membranes by phosphatidylinositol-specific phospholipase C. Biochemistry 1990; 29: 5405-5412.
149. Rogers M, Yehiely F, Scott M and Prusiner SB. Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells. Proc Natl Acad Sci U S A 1993; 90: 3182-3186.
150. Kocisko DA, Come JH, Priola SA, Chesebro B, Raymond GJ, Lansbury PT and Caughey B. Cellfree formation of protease-resistant prion protein. Nature 1994; 370: 471-474.
151. Chesebro B, Trifilo M, Race R, Meade-White K, Teng C, LaCasse R, Raymond L, Favara C, Baron G, Priola S, Caughey B, Masliah E and Oldstone M. Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 2005; 308: 1435-1439.
152. Trifilo MJ, Sanchez-Alavez M, Solforosi L, Bernard-Trifilo J, Kunz S, McGavern D and Oldstone MB. Scrapie-induced defects in learning and memory of transgenic mice expressing anchorless prion protein are associated with alterations in the gamma aminobutyric acidergic pathway. J Virol 2008; 82: 9890-9899.
153. Chesebro B, Race B, Meade-White K, Lacasse R, Race R, Klingeborn M, Striebel J, Dorward D, McGovern G and Jeffrey M. Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring. PLoS Pathog 2010; 6: e1000800.
154. Ghetti B, Tagliavini F, Takao M, Bugiani O and Piccardo P. Hereditary prion protein amyloidoses. Clin Lab Med 2003; 23: 65-85, viii.
155. Jansen C, Parchi P, Capellari S, Vermeij AJ, Corrado P, Baas F, Strammiello R, van Gool WA, van Swieten JC and Rozemuller AJ. Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP. Acta Neuropathol 2010; 119: 189-197.
156. Saftig P and Reiss K. The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential? Eur J Cell Biol 2011; 90: 527-535.