Résumés
Résumé
La protéine prion joue un rôle majeur dans le déclenchement et la transmission des encéphalopathies spongiformes subaiguës transmissibles. Au cours de la maladie, cette protéine adopte une conformation différente lui conférant des propriétés biochimiques nouvelles. En dépit d’avancées significatives, il existe encore de nombreuses incertitudes concernant la fonction normale de la protéine prion et les mécanismes impliqués dans la neurodégénérescence liée à la maladie. Cet article détaille les récents développements de la biologie de la protéine prion tels que la description de nouvelles formes topologiques de la molécule, sa localisation dans des compartiments cellulaires multiples et ses interactions potentielles avec des partenaires. Toutes ces données semblent essentielles pour la compréhension des fonctions physiologiques et pathologiques de la protéine.
Summary
Transmissible spongiform encephalopathies form a group of fatal neurodegenerative disorders represented principally by Creutzfeldt-Jakob disease in humans, and by scrapie and bovine spongiform encephalopathy in animals. Also called prion diseases, these disorders are infectious, sporadic, or genetic in origin. Although the nature of the responsible agent of these diseases is uncertain, it is clear that a protein called PrPSc plays a central role in their pathology. PrPSc is a conformational variant of a normal protein called PrPC. PrPC is a glycoprotein expressed by most tissues and is attached on the cell membrane through a glycosyl-phosphatidylinositol anchor, which is consistent with roles in cell adhesion, ligand uptake, or transmembrane signaling. NMR studies revealed that the protein has a globular domain and a long amino-terminal tail that contains repeated octapeptide domains, which bind metal ions with high affinities. PrPC is localized on the cell membrane in detergent resistant microdomains and may be part of functional complexes with other molecules such as N-CAM, Laminin or kinases. This is particularly relevant in view of the possible role of the molecule in signal transduction, resistance to oxidative stress and neuronal survival. The description both in vitro and in vivo, of a transmembrane form of PrP that can accumulate in the endoplasmic reticulum has attracted a lot of attention. The role of such isoforms in neurodegeneration, as well as the presence of PrP into the cytoplasm and in the nucleus where it may interact with nucleic acids are still debated. In conclusion, it appeared that the understanding of the PrP biology is essential to the understanding of the physiological function of this protein as well as for its pathological conversion since its trafficking governs the generation of PrPSc.
Parties annexes
Références
- 1. Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science 1982; 216: 136-44.
- 2. Prusiner SB, Scott MR, Dearmond SJ, Cohen FE. Prion protein biology. Cell 1998; 93: 337-48.
- 3. Sparkes RS, Simon M, Cohn VH, et al. Assignment of the human and mouse prion protein genes to homologous chromosomes. Proc Natl Acad Sci USA 1986; 83: 7358-62.
- 4. Manson J, West JD, Thomson V, et al. The prion protein gene: a role in mouse embryogenesis? Development 1992; 115: 117-22.
- 5. Puckett C, Concannon P, Casey C, Hood L. Genomic structure of the human prion protein gene. Am J Hum Genet 1991; 49: 320-9.
- 6. Ma J, Lindquist S. Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation. Proc Natl Acad Sci USA 2001; 98: 14955-60.
- 7. Donne DG, Viles JH, Groth D, et al. Structure of the recombinant full-length hamster prion protein PrP (29-231): the N-terminus is highly flexible. Proc Natl Acad Sci USA 1997; 94: 13452-7.
- 8. Riek R, Hornemann S, Wider G, et al. NMR structure of the mouse prion protein domain PrP (121-231). Nature 1996; 382: 180-2.
- 9. Hegde RS, Mastrianni JA, Scott MR, et al. A transmembrane form of the prion protein in neurodegenerative disease. Science 1998; 279: 827-34.
- 10. Stewart RS, Harris DA. Most pathogenic mutations do not alter the membrane topology of the prion protein. J Biol Chem 2001; 276: 2212-20.
- 11. Hay B, Barry RA, Lieberburg I, Prusiner SB, Lingappa VR. Biogenesis and transmembrane orientation of the cellular isoform of the scrapie prion protein. Mol Cell Biol 1987; 7: 914-20.
- 12. Hegde RS, Tremblay P, Groth D, et al. Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature 1999; 402: 822-6.
- 13. Stewart RS, Drisaldi B, Harris DA. A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic reticulum. Mol Biol Cell 2001; 12: 881-9.
- 14. Kim SJ, Rahbar R, Hegde RS. Combinatorial control of prion protein biogenesis by the signal sequence and transmembrane domain. J Biol Chem 2001; 276: 26132-40.
- 15. Hegde RS, Voigt S, Lingappa VR. Regulation of protein topology by trans-acting factors at the endoplasmic reticulum. Mol Cell 1998; 2: 85-91.
- 16. Coux O, Piechaczyk M. Le système ubiquitine/protéasome: un ensemble (de) complexe(s) pour dégrader les protéines. Med Sci 2000; 16: 623-9.
- 17. Zanusso G, Petersen RB, Jin T, et al. Proteasomal degradation and N-terminal protease resistance of the codon 145 mutant prion protein. J Biol Chem 1999; 274: 23396-404.
- 18. Yedidia Y, Horonchik L, Tzaban S, Yanai A, Taraboulos A. Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein. EMBO J 2001; 20: 5383-91.
- 19. Pfeifer K, Bachmann M, Schroder HC, Forrest J, Muller WE. Kinetics of expression of prion protein in uninfected and scrapie- infected N2a mouse neuroblastoma cells. Cell Biochem Funct 1993; 11 : 1-11.
- 20. Jaegly A, Mouthon F, Peyrin JM, et al. Search for a nuclear localization signal in the prion protein. Mol Cell Neurosci 1998; 11: 127-33.
- 21. Rybner C, Finel-Szermanski S, Felin M, et al. The cellular prion protein: a new partner of the lectin CBP70 in the nucleus of NB4 human promyelocytic leukemia cells. J Cell Biochem 2002; 84: 408-19.
- 22. Gilch S, Winklhofer KF, Groschup MH, et al. Intracellular re-routing of prion protein prevents propagation of PrP (Sc) and delays onset of prion disease. EMBO J 2001; 20: 3957-66.
- 23. Lehmann S, Milhavet O, Mange A. Trafficking of the cellular isoform of the prion protein. Biomed Pharmacother 1999; 53: 39-46.
- 24. Madore N, Smith KL, Graham CH, et al. Functionally different GPI proteins are organized in different domains on the neuronal surface. EMBO J 1999; 18: 6917-26.
- 25. Shyng SL, Heuser JE, Harris DA. A glycolipid-anchored prion protein is endocytosed via clathrin-coated pits. J Cell Biol 1994; 125: 1239-50.
- 26. Shyng SL, Moulder KL, Lesko A, Harris DA. The N-terminal domain of a glycolipid-anchored prion protein is essential for its endocytosis via clathrin-coated pits. J Biol Chem 1995; 270: 14793-800.
- 27. Shyng SL, Huber MT, Harris DA. A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. J Biol Chem 1993; 268: 15922-8.
- 28. Vincent B, Paitel E, Frobert Y, et al. Phorbol ester-regulated cleavage of normal prion protein in HEK293 human cells and murine neurons. J Biol Chem 2000; 275: 35612-6.
- 29. Vincent B, Paitel E, Saftig P, et al. 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: 37743-6.
- 30. Chen SG, Teplow DB, Parchi P, et al. Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem 1995; 270: 19173-80.
- 31. McMahon HE, Mange A, Nishida N, et al. Cleavage of the amino-terminus of the prion protein by reactive oxygen species. J Biol Chem 2001; 276: 2286-91.
- 32. Bueler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie. Cell 1993; 73: 1339-47.
- 33. Bueler H, Fischer M, Lang Y, et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 1992; 356: 577-82.
- 34. Manson JC, Clarke AR, Hooper ML, et al. 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal. Mol Neurobiol 1994; 8: 121-7.
- 35. Sakaguchi S, Katamine S, Nishida N, et al. Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature 1996; 380: 528-31.
- 36. Moore RC, Lee IY, Silverman GL, et al. Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel. J Mol Biol 1999; 292: 797-817.
- 37. Hornshaw MP, McDermott JR, Candy JM, Lakey JH. Copper binding to the N-terminal tandem repeat region of mammalian and avian prion protein: structural studies using synthetic peptides. Biochem Biophys Res Commun 1995; 214: 993-9.
- 38. Viles JH, Cohen FE, Prusiner SB, et al. Copper binding to the prion protein: structural implications of four identical cooperative binding sites. Proc Natl Acad Sci USA 1999; 96: 2042-7.
- 39. Kramer ML, Kratzin HD, Schmidt B, et al. Prion protein binds copper within the physiological concentration range. J Biol Chem 2001; 276: 16711-9.
- 40. Jackson GS, Murray I, Hosszu LL, et al. Location and properties of metal-binding sites on the human prion protein. Proc Natl Acad Sci USA 2001; 3 : 3.
- 41. Brown DR, Qin K, Herms JW, et al. The cellular prion protein binds copper in vivo. Nature 1997; 390: 684-7.
- 42. Pauly PC, Harris DA. Copper stimulates endocytosis of the prion protein. J Biol Chem 1998; 273: 33107-10.
- 43. Waggoner DJ, Drisaldi B, Bartnikas TB, et al. Brain copper content and cuproenzyme activity do not vary with prion protein expression level. J Biol Chem 2000; 275: 7455-8.
- 44. Brown DR, Besinger A. Prion protein expression and superoxide dismutase activity. Biochem J 1998; 334: 423-9.
- 45. Brown DR, Wong BS, Hafiz F, et al. Normal prion protein has an activity like that of superoxide dismutase. Biochem J 1999; 344: 1-5.
- 46. Milhavet O, McMahon HE, Rachidi W, et al. Prion infection impairs the cellular response to oxidative stress. Proc Natl Acad Sci USA 2000; 97: 13937-42.
- 47. Gabus C, Derrington E, Leblanc P, et al. The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1. J Biol Chem 2001; 276: 19301-9.
- 48. Gauczynski S, Peyrin JM, Haik S, et al. The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J 2001; 20: 5863-75.
- 49. Mouillet-Richard S, Ermonval M, Chebassier C, et al. Signal transduction through prion protein. Science 2000; 289: 1925-8.
- 50. Ostlund P, Lindegren H, Pettersson C, Bedecs K. Altered insulin receptor processing and function in scrapie-infected neuroblastoma cell lines. Brain Res Mol Brain Res 2001; 97: 161-70.
- 51. Lee IY, Westaway D, Smit AF, et al. Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res 1998; 8: 1022-37.
- 52. Baybutt H, Manson J. Characterisation of two promoters for prion protein (PrP) gene expression in neuronal cells. Gene 1997; 184: 125-31.
- 53. Martins VR, Graner E, Garcia-Abreu J, et al. Complementary hydropathy identifies a cellular prion protein receptor. Nat Med 1997; 3: 1376-82.
- 54. Yehiely F, Bamborough P, Da Costa M, et al. Identification of candidate proteins binding to prion protein. Neurobiol Dis 1997; 3: 339-55.
- 55. Kurschner C, Morgan JL. The cellular prion protein (PrP) selectively binds to Bcl-2 in the yeast two-hybrid system Brain Res Mol Brain Res 1995; 30: 165-8
- 56. Oesch B, Teplow DB, Stahl N, et al. Identification of cellular proteins binding to the scrapie prion protein. Biochemistry 1990; 29 : 5848-55.
- 57. Spielhaupter C, Schatzl HM. PrPC directly interacts with proteins involved in signaling pathways. J Biol Chem 2001; 276: 44604-12.
- 58. Edenhofer F, Rieger R, Famulok M, Wendler W, Weiss S, Winnacker EL. Prion protein PrPc interacts with molecular chaperones of the Hsp60 family. J Virol 1996; 70: 4724-8.
- 59. Graner E, Mercadante AF, Zanata SM, et al. Cellular prion protein binds laminin and mediates neuritogenesis. Brain Res Mol Brain Res 2000; 76: 85-92.
- 60. Rieger R, Edenhofer F, Lasmezas CI, Weiss S. The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nat Med 1997; 3 : 1383-8.
- 61. Schmitt-Ulms G, Legname G, Baldwin MA, et al. Binding of neural cell adhesion molecules (N-CAMs) to the cellular prion protein. J Mol Biol 2001; 314: 1209-25
- 62. Fischer MB, Roeckl C, Parisek P, et al. Binding of disease-associated prion protein to plasminogen. Nature 2000; 408 : 479-83.
- 63. Weiss S, Proske D, Neumann M, et al. RNA aptamers specifically interact with the prion protein PrP. J Virol 1997; 71 : 8790-7.
- 64. Ma J, Lindquist S. Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol. Science 2002 (online).
- 65. Ma J, Wollmann R, Lindquist S. Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol. Science 2002 (online).
- 66. Beranger F, Mangé A, Goud B, Lehmann S. Stimulation of PrPC retrograde transport toward the endoplasmic reticulum increases accumulation of PrPSc in prion-infected cells. J Biol Chem 2002; 277 : 38972-7.