Abstract
Studies on the transmission from man to animals of Creutzfeld-Jacob disease (CJD) led Prusiner to identify a proteinaceous infectious particle lacking nucleic acid, which was called prion. The identification of the infectious prion (PrPsc) then led to the discovery of the normal cellular counterpart (PrPc). One of the still enigmatic aspects regarding prion diseases is actually how, where, and when the transformation PrPc/PrPsc is occurring, this being due to the result of a large extent to the fact that so far most studies have been dedicated to the formation and transmission of PrPsc, whereas the understanding of physiologic roles of PrPc are in their infancy. In this review, we hope to identify the most reliable hypotheses for future experiments on PrPc. This is relevant not only for the understanding of PrPc functions but also to unravel the enigmatic nature of PrPc/PrPsc conversion.
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References
Prusiner, S. B. (1998) Prions. Proc. Natl. Acad. Sci. USA 95, 13363–13383.
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.
True, H. L. and Lindquist, S. L. (2000) A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407, 477–483.
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 neuro blastoma cells. J. Biol. Chem. 268, 15922–15928.
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.
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.
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.
Simons, K. and Toomre, D. (2000) Lipid rafts and signal transduction. Natl. Rev. Mol. Cell Biol. 1, 31–39.
Kurzchalia, T. V. and Parton, R. G. (1999) Membrane microdomains and caveolae. Curr. Opin. Cell Biol. 11, 424–431.
Tomasi, V., Spisni, E., Griffoni, C., and Guarnieri, T. (2000) Caveolae, caveolar enzymes and angiogenesis. Curr. Top. Biochem. Res. 3, 81–90.
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.
Okamoto, T., Schlegel, A., Scherer, P. E., and Lisanti, M. P. (1998) Caveolins, a family of scaffolding proteins for organizing “pressembled signaling complexes” at the plasma membrane. J. Biol. Chem. 273, 5419–5422.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lipardi, C., Mora, R., Colomer, V., et al. (1998) Caveolin transfection results in caveolae for-mation but not apical sorting of glycosylphos-phatidylinositol (GPI)-anchored proteins in epithelial cells. J. Cell. Biol. 140, 617–626.
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.
Shaul, P. W. and Anderson, R. G. (1998) Role of plasmalemmal caveolae in signal transduction. Am. J. Physiol. 275, L843-L851.
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.
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.
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.
Mouillet-Richard, S., Ermonval, M., Chebassier, C., et al. (2000) Signal transduction through prion protein. Science 289, 1925–1928.
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.
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.
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.
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.
Stuermer, C. A., Lang, D. M., Kirsch, F., Wiechers, M., Deininger, S. O., and Plattner, H. (2001). Glycosylphosphatidyl inositolanchored proteins and fyn kinase assemble in noncaveolar plasma membrane microdomains defined by reggie-1 and-2. Mol. Biol. Cell. 12, 3031–3045.
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.
Razani, B. and Lisanti, M. P. (2001) Caveolin-deficient mice: insights into caveolar function human disease. J. Clin. Invest. 108, 1553–15561.
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.
Collinge, J. (2001) Prion diseases of humans and animals: their causes and molecular basis. Annu. Rev. Neurosci. 24, 519–550.
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 prion protein. J. Mol. Biol. 289, 1163–1178.
Strumbo, B., Ronchi, S., Bolis, L. C., and Simonic, T. (2001) Molecular cloning of the cDNA coding for Xenopus laevis prion protein. FEBS Lett. 508, 170–174.
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.
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.
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.
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, 77–774.
Vilotte, J. L. and Laude, H. (2002) Transgenesis applied to transmissible spongiform encephalopathies, Transgenic Res. 11, 547–564.
Kaneko, K., Zulianello, L., Scott, M., et al. (1997) Evidence for protein X binding to a dis-continuous epitope on the cellular prion protein during scrapie prion propagation. Proc. Natl. Acad. Sci. USA 16, 10069–10074.
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.
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.
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.
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 neurode-generation. Nature 402, 822–826.
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.
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.
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.
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.
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.
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.
Gu, Y., Fujioka, H., Mishra, R. S., Li, R. and Singh, N. (2002) Prion peptide 106–126 modulates the aggregation of cellular prion protein and induces the synthesis of potentially neuro-toxic transmembrane PrP. J. Biol. Chem. 277, 2275–2286.
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.
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.
Mastrangelo, P. and Westaway, D. (2001) Biology of the prion gene complex. Biochem. Cell Biol. 79, 613–628.
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.
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.
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.
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.
Davies, S. and Ramsden, D. B. (2001) Huntington's disease. Mol. Pathol. 54, 409–413.
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.
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.
Colling, S. B., Collinge, J., and Jefferys, J. G. (1996) Hippocampal slices from prioin protein null mice: disrupted Ca(2+)-activated K+ currents. Neurosci. Lett. 209, 49–52.
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.
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.
Herms, J., Tings, T., Gall, S., et al. (1999) Evidence of presynaptic location and function of the prion protein. J. Neurosci. 19, 8866–8875.
Fournier, J. G., Tscaig-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.
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.
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.
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.
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.
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.
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.
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.
Hope, J. (2000) Prions and neurodegenerative diseases. Curr. Opin. Genet. Dev. 10, 568–574.
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.
Satoh, J., Kuroda, Y., and Katamine S. (2000) Gene expression profile in prion protein-deficient fibroblasts in culture. Am. J. Pathol. 157, 59–68.
Kuwahara, C., Takeuchi, A. M., Nishimura, T., et al. (1999) Prions prevent neuronal cell-line death. Nature 400, 225–226.
Chiarini, L. B., Freitas, A. R., Zanata, S. M., et al. (2002) Cellular prion protein transduces neuroprotective signals. EMBO J. 21, 3317–3326.
Zanata, S. M., Lopes, M. H., Mercadante, A. F., et al. (2002) Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection. EMBO J. 21, 3307–3316.
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.
Bounhar, Y., Zhang, Y., Goodyer, C. G., and LeBlanc, A. (2001) Prion protein protects human neurons against Bax-mediated apoptosis. J. Biol. Chem., 276C, 39145–39149.
White, A. R., Guirguis, R., Brazier M. W., et al. (2001) Sublethal concentrations of prion peptide PrP106-126 or the anyloid beta peptide of Alzheimer's disease activates expression of proapoptotic markers in primary cortical neurons. Neurobiol. Dis. 8, 299–316.
Weissmann, C., and Aguzzi A. (1999) Perspectives: neurobiology. PrP's double causes trouble. Science 286, 914–915.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Brown, D. R. (2000) PrPSc-like prion protein peptide inhibits the function of cellular prion protein. Biochem. J. 352, 511–518.
Brown, D. R., Qin, K., Herms, J. W., et al. (1997) The cellular prion protein binds copper in vivo. Nature 390, 684–687.
Wong, B. S., Pan, T., Liu, T., et al. (2000) Prion disease: a loss of antioxidant function? Biochem. Biophys. Res. Commun. 275, 249–252.
Pauly, P. C. and Harris, D. A. (1998) Copper stimulates endocytosis of the prion protein. J. Biol. Chem. 273, 33107–33110.
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.
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.
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.
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.
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.
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.
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.
Peretz, D., Williamson, R. A., Kaneko, K., et al. (2001) Artibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412, 739–743.
Shin, J. S. and Abraham, S. N. (2001) Co-option of endocytic functions of cellular caveolae by pathogens. Immunology 102, 2–7.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Stockel, J. and Hartl, F. U. (2001) Chaperonin-mediated de novo generation of prion protein aggregates. J. Mol. Biol. 313, 861–872.
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.
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.
Spielhaupter, C. and Schatzl, H. M. (2001) PrPc directly interacts with proteins involved in signaling pathways. J. Biol. Chem. 276, 44604–44612
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Griffoni, C., Toni, M., Spisni, E. et al. The cellular prion protein. Cell Biochem Biophys 38, 287–304 (2003). https://doi.org/10.1385/CBB:38:3:287
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DOI: https://doi.org/10.1385/CBB:38:3:287