1887

Abstract

PrP is a host-encoded glycoprotein involved in the pathogenesis of transmissible spongiform encephalopathies (TSEs) or ‘prion’ diseases. The normal form of the protein (PrP(C)) is heavily but incompletely glycosylated; it shows structural diversity in three neuroanatomically distinct regions of the brain. No effect of TSE infection on PrP(C) glycosylation has been detected. TSE-specific forms of PrP (PrP(Sc)) vary in their degree of glycosylation according to strain of TSE infectious agent. PrP(Sc) also varies independently in the amount and pattern of glycosylation according to brain region. This diversity shows that the glycosylation of PrP is under both host- and TSE agent-specified control, probably within the biosynthetic pathway for protein N-glycosylation. These findings challenge assumptions that PrP(Sc) is formed from the normal, mature form of PrP(Sc) but are compatible with a model in which the glycosylation phenotype of PrP(Sc) is under the control of both host cellular factors and TSE agent-specified information.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-7-1865
1999-07-01
2024-05-12
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/7/0801865a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-7-1865&mimeType=html&fmt=ahah

References

  1. Aguzzi A., Weissmann C. 1997; Prion research: the next frontiers. Nature 389:795–798
    [Google Scholar]
  2. Bruce M. E., Will R. G., Ironside J. W., McConnell I., Drummond D., Suttie A., McCardle L., Chree A., Hope J., Birkett C., Cousens S., Fraser H., Bostock C. J. 1997; Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389:498–501
    [Google Scholar]
  3. Caughey B. 1993; Scrapie associated PrP accumulation and its prevention: insights from cell culture. British Medical Bulletin 49:860–872
    [Google Scholar]
  4. Caughey B., Raymond G. J. 1991; The scrapie–associated form of PrP is made from a cell surface precursor that is both protease– and phospholipasesensitive. Journal of Biological Chemistry 266:18217–18223
    [Google Scholar]
  5. Collinge J., Sidle K. C. L., Meads J., Ironside J., Hill A. F. 1996; Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383:685–690
    [Google Scholar]
  6. DeArmond S. J., Sanchez H., Yehiely F., Qiu Y., Ninchak-Casey A., Daggett V., Camerino A. P., Cayetano J., Rogers M., Groth D., Torchia M., Tremblay P., Scott M. R., Cohen F. E., Prusiner S. B. 1997; Selective neuronal targeting in prion disease. Neuron 19:1337–1348
    [Google Scholar]
  7. Dickinson A. G., Meikle V. M. 1971; Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Molecular and General Genetics 112:73–79
    [Google Scholar]
  8. Endo T., Groth D., Prusiner S. B., Kobata A. 1989; Diversity of oligosaccharide structures linked to asparagines of the scrapie prion protein. Biochemistry 28:8380–8388
    [Google Scholar]
  9. Farquhar C. F., Dornan J., Somerville R. A., Tunstall A. M., Hope J. 1994; Effect of Sinc genotype, agent isolate and route of infection on the accumulation of protease–resistant PrP in non–central nervous system tissues during the development of murine scrapie. Journal of General Virology 75:495–504
    [Google Scholar]
  10. Farquhar C. F., Somerville R. A., Bruce M. E. 1998; Straining the prion hypothesis. Nature 391:345–346
    [Google Scholar]
  11. Hill A. F., Sidle K. C., Joiner S., Keyes P., Martin T. C., Dawson M., Collinge J. 1998; Molecular screening of sheep for bovine spongiform encephalopathy. Neuroscience Letters 255:159–162
    [Google Scholar]
  12. Hill A. F., Butterworth R. J., Joiner S., Jackson G., Rossor M. N., Thomas D. J., Frosh A., Tolley N., Bell J. E., Spencer M., King A., Al-Sarraj S., Ironside J. W., Lantos P. L., Collinge J. 1999; Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353:183–189
    [Google Scholar]
  13. Hope J., Morton L. J. D., Farquhar C. F., Multhaup G., Beyreuther K., Kimberlin R. H. 1986; The major polypeptide of scrapie-associated fibrils (SAF) has the same size, charge distribution and N– terminal protein sequence as predicted for the normal brain protein (PrP). EMBO Journal 5:2591–2597
    [Google Scholar]
  14. Hope J., Multhaup G., Reekie L. J., Kimberlin R. H., Beyreuther K. 1988; Molecular pathology of scrapie–associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie. European Journal of Biochemistry 172:271–277
    [Google Scholar]
  15. Hope J., Wood S. C. E. R., Birkett C. R., Chong A., Bruce M. E., Cairns D., Goldmann W., Hunter N., Bostock C. J. 1999; Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. Journal of General Virology 80:1–4
    [Google Scholar]
  16. Jeffrey M., Goodsir C. M., Bruce M. E., McBride P. A., Fowler N., Scott J. R. 1994; Murine scrapie–infected neurons in vivo release excess prion protein into the extracellular space. Neuroscience Letters 174:39–42
    [Google Scholar]
  17. Kascsak R. J., Rubenstein R., Merz P. A., Carp R. I., Wisniewski H. M., Diringer H. 1985; Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents. Journal of General Virology 66:1715–1722
    [Google Scholar]
  18. Kocisko D. A., Come J. H., Priola S. A., Chesebro B., Raymond G. J., Lansbury P. T., Caughey B. 1994; Cell–free formation of protease-resistant prion protein. Nature 370:471–474
    [Google Scholar]
  19. Kooyman D. L., Byrne G. W., McClellan S., Nielsen D., Tone M., Waldmann H., Coffman T. M., McCurry K. R., Platt J. L., Logan J. S. 1995; In vivo transfer of GPI–linked complement restriction factors from erythrocytes to the endothelium. Science 269:89–92
    [Google Scholar]
  20. Korth C., Stierli B., Streit P., Moser M., Schaller O., Fischer R., Schulz-Schaeffer W., Kretzschmar H., Raeber A., Braun U., Ehren-sperger F., Hornemann S., Glockshuber R., Riek R., Billeter M., Wuthrich K., Oesch B. 1997; Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390:74–77
    [Google Scholar]
  21. Kuczius T., Haist I., Groschup M. H. 1998; Molecular analysis of bovine spongiform encephalopathy and scrapie strain variation. Journal of Infectious Diseases 178:693–699
    [Google Scholar]
  22. Lehmann S., Harris D. A. 1997; Blockade of glycosylation promotes acquisition of scrapie–like properties by the prion protein in cultured cells. Journal of Biological Chemistry 272:21479–21487
    [Google Scholar]
  23. Meyer R. K., McKinley M. P., Bowman K. A., Braunfeld M. B., Barry R. A., Prusiner S. B. 1986; Separation and properties of cellular and scrapie prion proteins. Proceedings of the National Academy of Sciences, USA 83:2310–2314
    [Google Scholar]
  24. Moore R. C., Hope J., McBride P. A., McConnell I., Selfridge J., Melton D. W., Manson J. C. 1998; Mice with gene targetted prion protein alterations show that Prnp, Sinc and Prni are congruent. Nature Genetics 18:118–125
    [Google Scholar]
  25. Neville D. M. Jr 1971; Molecular weight determination of protein– dodecyl sulfate complexes by gel electrophoresis in a discontinuous buffer system. Journal of Biological Chemistry 246:6328–6334
    [Google Scholar]
  26. Oesch B., Westaway D., Walchli M., McKinley M. P., Kent S. B., Aebersold R., Barry R. A., Tempst P., Teplow D. B., Hood L. E., Prusiner S. B., Weissmann C. 1985; A cellular gene encodes scrapie PrP 27–30 protein. Cell 40:735–746
    [Google Scholar]
  27. O’Farrell P.Z., Goodman H.M., O’Farrell P.H. 1977; High resolution two–dimensional electrophoresis of basic as well as acidic proteins. Cell 12:1133–1141
    [Google Scholar]
  28. Oliver C., Essner E. 1973; Distribution of anomalous lysosomes in the beige mouse: a homologue of Chediak–Higashi syndrome. Journal of Histochemistry and Cytochemistry 21:218–228
    [Google Scholar]
  29. Parchi P., Castellani R., Capellari S., Petersen R. B., Chen S. G., Young K., Farlow M., Trojanowski J. Q., Sima A., Ghetti B., Gambetti P. 1995; Protease-resistant prion protein in sporadic Creutzfeldt Jakob disease (CJD): correlation with clinicopathological features and PrP genotype. Journal of Neuropathology & Experimental Neurology 54:416
    [Google Scholar]
  30. Parekh R. B., Dwek R. A., Thomas J. R., Opdenakker G., Rade-macher T. W., Wittwer A. J., Howard S. C., Nelson R., Siegel N. R., Jennings M. G., Harakas N., Feder J. 1989; Cell-type-specific and site-specific N-glycosylation of type I and type II human tissue plasminogen activator. Biochemistry 28:7644–7662
    [Google Scholar]
  31. Prusiner S. B. 1991; Molecular biology of prion diseases. Science 252:1515–1522
    [Google Scholar]
  32. Prusiner S. B. 1997; Prion diseases and the BSE crisis. Science 278:245–251
    [Google Scholar]
  33. Rubenstein R., Merz P. A., Kascsak R. J., Scalici C. L., Papini M. C., Carp R. I., Kimberlin R. H. 1991; Scrapie-infected spleens: analysis of infectivity, scrapie–associated fibrils, and protease-resistant proteins. Journal of Infectious Diseases 164:29–35
    [Google Scholar]
  34. Somerville R. A. 1991; The transmissible agent causing scrapie must contain more than protein. Reviews in Medical Virology 1:131–139
    [Google Scholar]
  35. Somerville R. A., Ritchie L. A. 1989; Are scrapie associated fibrils a pathological product of infection?. In Unconventional Virus Diseases of the Central NervousSystem pp 521–535 Edited by Court L. A., Dormont D., Brown P., Kingsbury D. T. Fauntenay-aux-Roses: Commisariat a lEnergie Atomique;
    [Google Scholar]
  36. Somerville R. A., Ritchie L. A. 1990; Differential glycosylation of the protein (PrP) forming scrapie–associated fibrils. Journal of General Virology 71:833–839
    [Google Scholar]
  37. Somerville R. A., Ritchie L. A., Gibson P. H. 1989; Structural and biochemical evidence that scrapie–associated fibrils assemble in vivo . Journal of General Virology 70:25–35
    [Google Scholar]
  38. Somerville R. A., Birkett C. R., Farquhar C. F., Hunter N., Goldmann W., Dornan J., Grover D., Hennion R. M., Percy C., Foster J., Jeffrey M. 1997a; Immunodetection of PrPSc in spleens of some scrapie–infected sheep but not BSE–infected cows. Journal of General Virology 78:2389–2396
    [Google Scholar]
  39. Somerville R. A., Chong A., Mulqueen O. U., Birkett C. R., Wood S. C. E. R., Hope J. 1997b; Biochemical typing of scrapie strains. Nature 386:564
    [Google Scholar]
  40. Stahl N., Borchelt D. R., Prusiner S. B. 1990a; Differential release of cellular and scrapie prion proteins from cellular membranes by phosphatidylinositol–specific phospholipase C. Biochemistry 29:540–55412
    [Google Scholar]
  41. Stahl N., Baldwin M. A., Burlingame A. L., Prusiner S. B. 1990b; Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein. Biochemistry 29:8879–8884
    [Google Scholar]
  42. Stahl N., Baldwin M. A., Teplow D. B., Hood L., Gibson B. W., Burlingame A. L., Prusiner S. B. 1993; Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry 32:1991–2002
    [Google Scholar]
  43. Suzuki T., Seko A., Kitajima K., Inoue Y., Inoue S. 1994; Purification and enzymatic properties of peptide:N–glycanase from C3H mouse-derived L-929 fibroblast cells. Possible widespread occurrence of post–translational remodification of proteins by N–deglycosylation. Journal of Biological Chemistry 269:17611–17618
    [Google Scholar]
  44. Towbin H., Staehelin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences, USA 764350–4354
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-7-1865
Loading
/content/journal/jgv/10.1099/0022-1317-80-7-1865
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error