The cellular prion protein: Biochemistry, topology, and physiologic functions

Cell Biochemistry and Biophysics

Volumn 38, Issue 3, 2003, Pages 287-304

  Griffoni, Cristiana ^a   Toni, Mattia ^a   Spisni, Enzo ^a   Bianco, Maria Cristina ^a   Santi, Spartaco ^b   Riccio, Massimo ^b   Tomasi, Vittorio ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b CNR   (Italy)

Author keywords

Caveolae; Copper binding; Prion protein; Rafts; Signal transduction

Indexed keywords

ANIMALIA;

CELL SURFACE RECEPTOR; COPPER; PRION PROTEIN;

ANIMAL; APOPTOSIS; BIOLOGICAL MODEL; CHEMISTRY; CREUTZFELDT JAKOB DISEASE; HUMAN; METABOLISM; MOUSE; PHYSIOLOGY; PROTEIN BINDING; PROTEIN CONFORMATION; REVIEW;

ANIMALS; APOPTOSIS; COPPER; CREUTZFELDT-JAKOB SYNDROME; HUMANS; MICE; MODELS, BIOLOGICAL; PROTEIN BINDING; PROTEIN CONFORMATION; PRPC PROTEINS; PRPSC PROTEINS; RECEPTORS, CELL SURFACE;

EID: 2142728575     PISSN: 10859195     EISSN: None     Source Type: Journal    
DOI: 10.1385/CBB:38:3:287     Document Type: Review

References (130)

1. Prusiner, S. B. (1998) Prions. Proc. Natl. Acad. Sci. USA 95, 13363-13383.
2. Rode, B. M., Flader, W., Sotriffer, C., and Righi, A. (1999) Are prions a relic of an early stage of peptide evolution? Peptides 20, 1513-1516.
3. True, H. L. and Lindquist, S. L. (2000) A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407, 477-483.
4. Shyng, S. L., Huber, M. T., and Harris, D. A. (1993) A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. J. Biol. Chem. 268, 15922-15928.
5. Lehmann, S. and Harris, D. A. (1995) A mutant prion protein displays an aberrant membrane association when expressed in cultured cells. J. Biol. Chem. 270, 24589-24597.
6. Stein, E., Lane, A. A., Cerretti, D. P., et al. (1998) Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev. 12, 667-678.
7. Kholodenko, B. N., Hoek, J. B., and Westerhoff, H. V. (2000) Why cytoplasmic signalling proteins should be recruited to cell membranes. Trends Cell Biol. 10, 173-178.
8. Simons, K. and Toomre, D. (2000) Lipid rafts and signal transduction. Natl. Rev. Mol. Cell Biol. 1, 31-39.
9. Kurzchalia, T. V. and Parton, R. G. (1999) Membrane microdomains and caveolae. Curr. Opin. Cell Biol. 11, 424-431.
10. Tomasi, V., Spisni, E., Griffoni, C., and Guarnieri, T. (2000) Caveolae, caveolar enzymes and angiogenesis. Curr. Top. Biochem. Res. 3, 81-90.
11. Massimino, M. L., Griffoni, C., Spisni, E., Toni, M., and Tomasi V. (2002) Involvement of caveolae and caveolae-like domains in signalling, cell survival and angiogenesis. Cell Signal 14, 93-98.
12. Okamoto, T., Schlegel, A., Scherer, P. E., and Lisanti, M. P. (1998) Caveolins, a family of scaffolding proteins for organizing "preassembled signaling complexes" at the plasma membrane. J. Biol. Chem. 273, 5419-5422.
13. Fra, A. M., Pasqualetto, E., Mancini, M., and Sitia, R. (2000) Genomic organization and transcriptional analysis of the human genes coding for caveolin-1 and caveolin-2. Gene 243, 75-83.
14. Schlegel, A. and Lisanti, M. P. (2000) A molecular dissection of caveolin-1 membrane attachment and oligomerization. Two separate regions of the caveolin-1 C-terminal domain mediate membrane binding and oligomer/oligomer interactions in vivo. J. Biol. Chem. 275, 21605-21617.
15. Sotgia, F., Lee, J. K., Das, K., et al. (2000) Caveolin-3 directly interacts with the C-terminal tail of beta -dystroglycan. Identification of a central WW-like domain within caveolin family members. J. Biol. Chem. 275, 38048-38058.
16. Matsuda, C., Hayashi, Y. K., Ogawa, M., et al. (2001) The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Hum. Mol. Genet. 10,1761-1766.
17. Tang, Z., Scherer, P. E., Okamoto, T., et al. (1996) Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle. J. Biol. Chem. 271, 2255-2261.
18. Herrmann, R., Straub, V., Blank, M., et al. (2000) Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy. Hum. Mol. Genet. 9, 2335-2340.
19. Vorgerd, M., Ricker, K., Ziemssen, F., et al. (2001) A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation. Neurology 57, 2273-2277.
20. Liu, J., Wang, X. B., Park, D. S., and Lisanti, M. P. (2002) Caveolin-1 expression enhances endothelial capillary tubule formation. J. Biol. Chem. 277, 10661-10668.
21. Iwabuchi, K., Handa, K., and Hakomori, S. (1998) Separation of "glycosphingolipid signaling domain" from caveolin-containing membrane fraction in mouse melanoma B16 cells and its role in cell adhesion coupled with signaling. J. Biol. Chem. 273, 33766-33773.
22. Lipardi, C., Mora, R., Colomer, V., et al. (1998) Caveolin transfection results in caveolae formation but not apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins in epithelial cells. J. Cell Biol. 140, 617-626.
23. Sowa, G., Pypaert, M., and Sessa, W. C. (2001) Distinction between signaling mechanisms in lipid rafts vs. caveolae. Proc. Natl. Acad. Sci. USA 98, 14072-14077.
24. Shaul, P. W. and Anderson, R. G. (1998) Role of plasmalemmal caveolae in signal transduction. Am. J. Physiol. 275, L843-L851.
25. Griffoni, C., Spisni, E., Santi, S., Riccio, M., Guarnirei, T., and Tomasi, V. (2000) Knockdown of caveolin-1 by antisense oligonucleotides impairs angiogenesis in vitro and in vivo. Biochem. Biophys. Res. Commun. 276, 756-761.
26. Abrami, L., Fivaz, M., Kobayashi, T., Kinoshita, T., Parton, R. G., and van der Goot, F.G. (2001) Cross-talk between caveolae and glycosylphosphatidylinositol-rich domains. J. Biol. Chem. 276, 30729-30736.
27. Vey, M., Pilkuhn, S., Wille, H., et al. (1996) Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains. Proc. Natl. Acad. Sci. USA 93, 14945-14949.
28. Mouillet-Richard, S., Ermonval, M., Chebassier, C., et al. (2000) Signal transduction through prion protein. Science 289, 1925-1928.
29. Braun, J. E. and Madison, D. V. (2000) A novel SNAP25-caveolin complex correlates with the onset of persistent synaptic potentiation. J. Neurosci. 20, 5997-6006.
30. Prioni, S., Liberto, N., Prinetti, A., et al. (2002) Sphingolipid metabolism and caveolin expression in gonadotropin-releasing hormone-expressing GN11 and gonadotropin-releasing hormone-secreting GT1-7 neuronal cells. Neurochem. Res. 27, 831-840.
31. Cameron, P. L., Liu, C., Smart, D. K., Hantus, S. T., Fick, J. R., and Cameron, R. S. (2002) Caveolin-1 expression is maintained in rat and human astroglioma cell lines. Glia 37, 275-290.
32. Volonte, D., Galbiati, F., Li, S., Nishiyama, K., Okamoto, T., and Lisanti, M. P. (1999) Flotillins/cavatellins are differentially expressed in cells and tissues and form a hetero-oligomeric complex with caveolins in vivo. Characterization and epitope-mapping of a novel flotillin-1 monoclonal antibody probe. J. Biol. Chem. 274, 12702-12709.
33. Stuermer, C.A., Lang, D. M., Kirsch, F., Wiechers, M., Deininger, S. O., and Plattner, H. (2001) Glycosylphosphatidyl inositol-anchored proteins and fyn kinase assemble in noncaveolar plasma membrane microdomains defined by reggie-1 and -2. Mol. Biol. Cell. 12, 3031-3045.
34. Razani, B., Engelman, J. A., Wang, X. B., et al. (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J. Biol. Chem. 276, 38121-38138.
35. Razani, B. and Lisanti, M. P. (2001) Caveolin-deficient mice: insights into caveolar function human disease. J. Clin. Invest. 108, 1553-15561.
36. Kimura, A., Baumann, C. A., Chiang, S. H., and Saltiel, A. R. (2001) The sorbin homology domain: a motif for the targeting of proteins to lipid rafts. Proc. Natl. Acad. Sci. USA 98, 9098-9103.
37. Collinge, J. (2001) Prion diseases of humans and animals: their causes and molecular basis. Annu. Rev. Neurosci. 24, 519-550.
38. Wopfner, F., Weidenhofer, G., Schneider, R., et al. (1999) Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of flexible regions of the priori protein. J. Mol. Biol. 289, 1163-1178.
39. Strumbo, B., Ronchi, S., Bolis, L.C., and Simonic, T. (2001) Molecular cloning of the cDNA coding for Xenopus laevis priori protein. FEBS Lett. 508, 170-174.
40. Beck, J.A., Mead, S., Campbell, T.A., et al. (2001) Two-octapeptide repeat deletion of prion protein associated with rapidly progressive dementia. Neurology 57, 354-356.
41. Palmer, M. S., Mahal, S. P., Campbell, T. A., et al. (1993) Deletions in the prion protein gene are not associated with CJD. Hum. Mol. Genet. 2, 541-544.
42. Meyer, R. K., Lustig, A., Oesch, B., Fatzer, R., Zurbriggen, A., and Vandevelde, M. (2000) A monomer-dimer equilibrium of a cellular prion protein (PrPc) not observed with recombinant PrP. J. Biol. Chem. 275, 38081-38087.
43. Knaus, K .J., Morillas, M., Swietnicki, W., Malone, M., Surewicz, W. K. and Yee, V. C. (2001) Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat. Struct. Biol 8, 770-774.
44. Vilotte, J. L. and Laude, H. (2002) Transgenesis applied to transmissible spongiform encephalopathies. Transgenic Res. 11, 547-564.
45. Kaneko, K., Zulianello, L., Scott, M., et al. (1997) Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation. Proc. Natl. Acad. Sci. USA 16, 10069-10074.
46. Kaneko, K., Vey, M., Scott, M., Pilkuhn, S., Cohen, F. E., and Prusiner, S. B. (1997) COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform. Proc. Natl. Acad. Sci. USA. 94, 2333-2338.
47. Holscher, C., Bach, U.C., and Dobberstein, B. (2001) Prion protein contains a second endoplasmic reticulum targeting signal sequence located at its C terminus. J. Biol. Chem. 276, 13388-13394.
48. Hegde, R. S., Mastrianni, J. A., Scott, M. R., et al. (1998) A transmembrane form of the prion protein in neurodegenerative disease. Science 279, 827-834.
49. Hegde, R. S., Tremblay, P., Groth, D., DeArmond, S. J., Prusiner, S. B., and Lingappa, V. R. (1999) Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature 402, 822-826.
50. Schmitt-Ulms, G., Legname, G., Baldwin, M. A., et al. (2001) Binding of neural cell adhesion molecules (N-CAMs) to the cellular prion protein. J. Mol. Biol. 314, 1209-1225.
51. Gauczynski, S., Peyrin, J. M., Haik, S., et al. (2001) The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J. 20, 5863-5875.
52. Keshet, G. I., Bar-Peled, O., Yaffe, D., Nudel, U., and Gabizon, R. (2000) The cellular prion protein colocalizes with the dystroglycan complex in the brain. J. Neurochem. 75, 1889-1897.
53. Rieger, R., Edenhofer, F., Lasmezas, C. I., and Weiss, S. (1997) The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cellsn. Nat. Med. 3, 1383-1388.
54. Martins, V. R., Mercadante, A. F., Cabral, A. L., Freitas, A. R., and Castro, R. M. (2001) Insights into the physiological function of cellular prion protein. Braz. J. Med. Biol. Res. 34, 585-595.
55. Kim, S. J., Rahbar, R., and Hegde, R. S. (2001) Combinatorial control of prion protein biogenesis by the signal sequence and transmembrane domain. J. Biol. Chem. 276, 26132-26140.
56. Gu, Y., Fujioka, H., Mishra, R. S., Li, R. and Singh, N. (2002) Priori peptide 106-126 modulates the aggregation of cellular priori protein and induces the synthesis of potentially neurotoxic transmembrane PrP. J. Biol. Chem. 277, 2275-2286.
57. Stewart, R. S., Drisaldi, B. and Harris, D. A. (2001) A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic reticulum. Mol. Biol. Cell 12, 881-889.
58. Moore, R. C., Lee, I. Y., Silverman, G. L., et al. (1999) Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel. J. Mol. Biol. 292, 797-817.
59. Mastrangelo, P. and Westaway, D. (2001) Biology of the prion gene complex. Biochem. Cell Biol. 79, 613-628.
60. Basler, K., Oesch, B., Scott, M., et al. (1986) Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46, 417-428.
61. Puckett, C., Concannon, P., Casey, C., and Hood, L. (1991) Genomic structure of the human prion protein gene. Am. J. Hum. Genet. 49, 320-329.
62. Lee, I. Y., Westaway, D., Smit, A. F., et al. (1998) Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res. 8, 1022-1037.
63. Horiuchi, M., Ishiguro, N., Nagasawa, H., Toyoda, Y., and Shinagawa, M. (1997) Alternative usage of exon 1 of bovine PrP mRNA. Biochem. Biophys. Res. Commun. 233, 650-654.
64. Davies, S. and Ramsden, D.B. (2001) Huntington's disease. Mol. Pathol. 54, 409-413.
65. Bueler, H., Fischer, M., Lang, Y., et al. (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356, 577-582.
66. Lledo, P. M., Tremblay, P., DeArmond, S. J., Prusiner, S. B., and Nicoll, R. A. (1996) Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the hippocampus. Proc. Natl. Acad. Sci. USA 93, 2403-2407.
67. Colling, S. B., Collinge, J., and Jefferys, J. G. (1996) Hippocampal slices from prion protein null mice: disrupted Ca(2+)-activated K+ currents. Neurosci. Lett. 209, 49-52.
68. Tobler, I., Gaus, S. E., Deboer, T., et al. (1996) Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 380, 639-642.
69. Mallucci, G. R., Ratte, S., Asante, E. A., Linehan, J., Gowland, I., Jefferys, J. G., and Collinge, J. (2002) Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration. EMBO J. 21, 202-210.
70. Herms, J., Tings, T., Gall, S., et al. (1999) Evidence of presynaptic location and function of the prion protein. J. Neurosci. 19, 8866-8875.
71. Fournier, J. G., Escaig-Haye, F., Billette de Villemeur, T., and Robain, O. Ultrastructural localization of cellular prion protein (PrPc) in synaptic boutons of normal hamster hippocampus. Can. R. Acad. Sci. 318, 339-344.
72. Collinge, J., Whittington, M. A., Sidle, K. C., Smith, C. J., Palmer, M. S., Clarke, A. R., and Jefferys, J. G. (1994) Prion protein is necessary for normal synaptic function. Nature 370, 295-297.
73. Askanas, V., Bilak, M., Engel, W. K., Leclerc, A., and Tome, F. (1993) Prion protein is strongly immunolocalized at the postsynaptic domain of human normal neuromuscular junctions. Neurosci. Lett. 159, 111-114.
74. Laine, J., Marc, M. E., Sy, M. S., and Axelrad, H. (2001) Cellular and subcellular morphological localization of normal prion protein in rodent cerebellum. Eur. J. Neurosci. 14, 47-56.
75. Nishida, N., Katamine, S., Shigematsu, K., et al. (1997) Prion protein is necessary for latent learning and long-term memory retention. Cell Mol. Neurobiol. 17, 537-545.
76. Whittington, M. A., Sidle, K. C., Gowland, I., et al. (1995) Rescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein. Nat. Genet. 9, 197-201.
77. Westaway, D., DeArmond, S. J., Cayetano-Canlas, J., et al. (1994) Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins. Cell 76, 117-129.
78. Shmerling, D., Hegyi, I., Fischer, M., et al. (1998) Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 93, 203-214.
79. Hope, J. (2000) Prions and neurodegenerative diseases. Curr. Opin. Genet. Dev. 10, 568-574.
80. Li, A., Sakaguchi, S., Atarashi, R., et al. (2000) Identification of a novel gene encoding a PrP-like protein expressed as chimeric transcripts fused to PrP exon 1/2 in ataxic mouse line with a disrupted PrP gene. Cell Mol. Neurobiol. 20, 553-567.
81. Satoh, J., Kuroda, Y., and Katamine S. (2000) Gene expression profile in prion protein-deficient fibroblasts in culture. Am. J. Pathol. 157, 59-68.
82. Kuwahara, C., Takeuchi, A. M., Nishimura, T., et al. (1999) Prions prevent neuronal cell-line death. Nature 400, 225-226.
83. Chiarini, L. B., Freitas, A. R., Zanata, S. M., et al. (2002) Cellular priori protein transduces neuroprotective signals. EMBO J. 21, 3317-3326.
84. Zanata, S. M., Lopes, M. H., Mercadante, A. F., et al. (2002) Stress-inducible protein 1 is a cell surface ligand for cellular priori that triggers neuroprotection. EMBO J. 21, 3307-3316.
85. Braun, J. E. and Madison, D. V. A novel SNAP25-caveolin complex correlates with the onset of persistent synaptic potentiation. J. Neurosci. 20, 5997-6006.
86. Bounhar, Y., Zharig, Y., Goodyer, C. G., and LeBlanc, A. (2001) Prion protein protects human neurons against Bax-mediated apoptosis. J. Biol. Chem. 276G, 39145-39149.
87. White, A.R., Guirguis, R., Brazier, M.W., et al. (2001) Sublethal concentrations of prion peptide PrP106-126 or the amyloid beta peptide of Alzheimer's disease activates expression of proapoptotic markers in primary cortical neurons. Neurobiol. Dis. 8, 299-316.
88. Weissmann, C., and Aguzzi, A. (1999) Perspectives: neurobiology. PrP's double causes trouble. Science 286, 914-915.
89. Silverman, G. L., Qin, K., Moore, R. C., et al. (2000) Doppel is an N-glycosylated, glycosylphosphatidylinositol-anchored protein. Expression in testis and ectopic production in the brains of Prnp(0/0) mice predisposed to Purkinje cell loss. J. Biol. Chem. 275, 26834-26841.
90. Sakaguchi, S., Katamine, S., Nishida, N., et al. (1996) Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature 380, 528-531.
91. Li, R., Liu, T., Wong, B. S., et al. (2000) Identification of an epitope in the C terminus of normal prion protein whose expression is modulated by binding events in the N terminus. J. Mol. Biol. 301, 567-573.
92. Moore, R. C., Mastrangelo, P., Bouzamondo, E., et al. (2001) Doppel-induced cerebellar degeneration in transgenic mice. Proc. Natl. Acad. Sci. USA 98, 15288-15293.
93. McKenzie, D., Bartz, J., Mirwald, J., Olander, D., Marsh, R., and Aiken, J. (1998) Reversibility of scrapie inactivation is enhanced by copper. J. Biol. Chem. 273, 25545-25547.
94. Wadsworth, J. D., Hill, A. F., Joiner, S., Jackson, G. S., Clarke, A. R., and Collinge, J. (1999) Strain-specific prion-protein conformation determined by metal ions. Nat. Cell Biol. 1, 55-59.
95. Whittal, R. M., Ball, H. L., Cohen, F. E., Burlingame, A. L., Prusiner, S. B., and Baldwin, M. A. (2000) Copper binding to octarepeat peptides of the prion protein monitored by mass spectrometry. Protein Sci. 9, 332-343.
96. Jackson, G. S., Murray, I., Hosszu, L. L., et al. (2001) Location and properties of metal-binding sites on the human prion protein. Proc. Natl. Acad. Sci. USA. 98, 8531-8535.
97. Kramer, M. L., Kratzin, H. D., Schmidt, B., et al. (2001) Prion protein binds copper within the physiological concentration range. J. Biol. Chem. 276, 16711-16719.
98. Hasnain, S. S., Murphy, L. M., Strange, R. W., et al. (2001) XAFS study of the high-affinity copper-binding site of human PrP(91-231) and its low-resolution structure in solution. J. Mol. Biol. 311, 467-473.
99. Cereghetti, G. M., Schweiger, A., Glockshuber, R., and Van Doorslaer, S. (2001) Electron paramagnetic resonance evidence for binding of Cu(2+) to the C-terminal domain of the murine prion protein. Biophys. J. 81, 516-525.
100. Thackray, A. M., Knight, R., Haswell, S. J., Bujdoso, R., and Brown, D. R. (2002) Metal imbalance and compromised antioxidant function are early changes in prion disease. Biochem. J. 362, 253-258.
101. Kretzschmar, H. A., Tings, T., Madlung, A., Giese, A., and Herms, J. (2000) Function of PrP(C) as a copper-binding protein at the synapse. Arch. Virol. Suppl. 16, 239-249.
102. Brown, D. R. (2000) PrPSc-like prion protein peptide inhibits the function of cellular prion protein. Biochem. J. 352, 511-518.
103. Brown, D. R., Qin, K., Herms, J. W., et al. (1997) The cellular prion protein binds copper in vivo. Nature 390, 684-687.
104. Wong, B. S., Pan, T., Liu, T., et al. (2000) Prion disease: a loss of antioxidant function? Biochem. Biophys. Res. Commun. 275, 249-252.
105. Pauly, P. C. and Harris, D. A. (1998) Copper stimulates endocytosis of the prion protein. J. Biol. Chem. 273, 33107-33110.
106. Viles, J. H., Cohen, F. E., Prusiner, S. B., Goodin, D. B., Wright, P. E., and Dyson, H. J. (1999) Copper binding to the prion protein: structural implications of four identical cooperative binding sites. Proc. Natl. Acad. Sci. USA 96, 2042-2047.
107. Waggoner, D. J., Drisaldi, B., Bartnikas, T. B., et al. (2000) Brain copper content and cuproenzyme activity do not vary with prion protein expression level. J. Biol. Chem. 275, 7455-7458.
108. Perera, W. S. and Hooper, N. M. (2001) Ablation of the metal ion-induced endocytosis of the prion protein by disease-associated mutation of the octarepeat region. Curr. Biol. 11, 519-523.
109. Lee, K. S., Magalhaes, A. C., Zanata, S. M., Brentani, R. R., Martins, V. R. and Prado, M. A. Internalization of mammalian fluorescent cellular prion protein and N-terminal deletion mutants in living cells. J. Neurochem. 79, 79-87.
110. Quaglio, E., Chiesa, R., and Harris, D. A. (2001) Copper converts the cellular prion protein into a protease-resistant species that is distinct from the scrapie isoform. J. Biol. Chem. 276, 11432-11438.
111. Mahfoud, R., Garmy N., Maresca, M., Yahi, N., Puigserver, A., and Fantini, J. (2002) Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins. J. Biol. Chem. 277, 11292-11296.
112. Heppner, F. L., Musahl, C., Arrighi, I., et al. (2001) Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies. Science 294, 178-182.
113. Peretz, D., Williamson, R. A., Kaneko, K., et al. (2001) Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412, 739-743.
114. Shin, J. S. and Abraham, S. N. (2001) Co-option of endocytic functions of cellular caveolae by pathogens. Immunology 102, 2-7.
115. Van Gool, W.A., Hensels, G. W., Hoogerwaard, E. M., Wiezer, J. H., Wesseling, P., and Bolhuis, P. A. (1995) Hypokinesia and presenile dementia in a Dutch family with a novel insertion in the prion protein gene. Brain 118, 1565-1571.
116. Duchen, L. W., Poulter, M., and Harding, A. E. (1993) Dementia associated with a 216 base pair insertion in the prion protein gene. Clinical and neuropathological features. Brain 116, 555-567.
117. Van Harten, B., van Gool, W. A., Van Langen, I. M., Deekman, J. M., Meijerink, P. H., and Weinstein, H. C. (2000) A new mutation in the prion protein gene: a patient with dementia and white matter changes. Neurology 55, 1055-1057.
118. Capellari, S., Vital, C., Parchi, P., et al. (1997) Familial prion disease with a novel 144-bp insertion in the prion protein gene in a Basque family. Neurology 49, 133-141.
119. Campbell, T. A., Palmer, M. S., Will, R. G., Gibb, W. R., Luthert, P. J., and Collinge, J. (1996) A prion disease with a novel 96-base pair insertional mutation in the prion protein gene. Neurology 46, 761-766.
120. Cochran, E. J., Bennett, D. A., Cervenakova, L., et al. (1996) Familial Creutzfeldt-Jakob disease with a five-repeat octapeptide insert mutation. Neurology 47, 727-733.
121. Skworc, K. H., Windl, O., Schulz-Schaeffer, W. J., et al. (1999) Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion protein gene. Ann. Neurol. 46, 693-700.
122. Krasemann, S., Zerr, I., Weber, T., et al. (1995) Prion disease associated with a novel nine octapeptide repeat insertion in the PRNP gene. Brain Res. Mol. Brain Res. 34, 173-176.
123. Rossi, G., Giaccone, G., Giampaolo, L., et al. (2000) Creutzfeldt-Jakob disease with a novel four extra-repeat insertional mutation in the PrP gene. Neurology 55, 405-410.
124. Goldfarb, L. G., Brown, P., McCombie, W. R., et al. (1991) Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. Proc. Natl. Acad. Sci. USA. 88, 10926-10930.
125. Goldfarb, L. G., Brown, P., Little, B. W., et al. (1993) A new (two-repeat) octapeptide coding insert mutation in Creutzfeldt-Jakob disease. Neurology 43, 2392-2394.
126. Telling, G. C., Scott, M., Mastrianni, J., et al. (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83, 79-90.
127. Stockel, J. and Hartl, F. U. (2001) Chaperonin-mediated de novo generation of prion protein aggregates. J. Mol. Biol. 313, 861-872.
128. Graner, E., Mercadante, A. F., Zanata, S. M., et al. (2000) Cellular prion protein binds laminin and mediates neuritogenesis. Mol. Brain Res. 76, 85-92.
129. Hundt, C., Peyrin, J. M., Haik, S., et al. (2001) Identification of interaction domains of the prion protein with its 37-kDa/67-kDa laminin receptor. EMBO J. 20, 5876-5886.
130. Spielhaupter, C. and Schatzl, H. M. (2001) PrPc directly interacts with proteins involved in signaling pathways. J. Biol. Chem. 276, 44604-44612.