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Complementary hydropathy identifies a cellular prion protein receptor

Nature Medicine volume 3, pages 1376–1382 (1997)Cite this article

Abstract

Prions, the etiological agents for infectious degenerative encephalopathies, act by entering the cell and inducing conformational changes in PrPc (a normal cell membrane sialoglycoprotein), which result in cell death. A specific cell-surface receptor to mediate PrPc and prion endocytosis has been predicted. Complementary hydropathy let us generate a hypothetical peptide mimicking the receptor binding site. Antibodies raised against this peptide stain the surface of mouse neurons and recognize a 66-kDa membrane protein that binds PrPc both in vitro and in vivo. Furthermore, both the complementary prion peptide and antiserum against it inhibit the toxicity of a prion-derived peptide toward neuronal cells in culture. Such reagents might therefore have therapeutic applications.

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References

  1. Prusiner, S.B. Genetic and infections prion diseases. Arch. Neurol. 50, 1129–1153 (1993).

    Article  CAS  Google Scholar 

  2. Prusiner, S.B. Molecular biology of prion diseases. Science 252, 1515–1522 (1991).

    Article  CAS  Google Scholar 

  3. Weissman, C. Molecular biology of prion diseases. Trends Cell Biol. 4, 10–14 (1994).

    Article  Google Scholar 

  4. Baster, K. et al. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46, 417–428 (1986).

    Article  Google Scholar 

  5. Pan, K.-M. et al. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc. Natl. Acad. Sci. USA 90, 10962–10966 (1993).

    Article  CAS  Google Scholar 

  6. Borchelt, D.R., Taraboulos, A. & Prusiner, S.B. Evidence for synthesis of scrapie prion proteins in endocytic pathway. J. Biol. Chem. 267, 16188–16199 (1992).

    CAS  PubMed  Google Scholar 

  7. Büeler, H. et al. Mice devoid of PrP are resistant to scrapie. Cell 73, 1339–1347 (1993).

    Article  Google Scholar 

  8. Shyng, S.-L., Heuser, J.E. & Harris, D.A. A glycolipid-anchored prion proteins endo cytosed via clathrin-coated pits. J. Cell Biol. 125, 1239–1250 (1994).

    Article  CAS  Google Scholar 

  9. Vey, M. et al. Subcellular colocalization of the cellular and scrapie priori proteins in caveolae-like membranous domains. Proc. Natl. Acad. Sci. USA 93, 14945–14949 (1996).

    Article  CAS  Google Scholar 

  10. Yehiely, F. et al. Identification of candidate proteins binding to prion protein. Neurobiol. Dis. 3, 339–355 (1997).

    Article  CAS  Google Scholar 

  11. Forloni, G. et al. Neurotoxicity of a prion protein fragment. Nature 362, 543–546 (1993).

    Article  CAS  Google Scholar 

  12. Shyng, S.-L., Moulder, K.J., Laesko, A. & Harris, D.A. The N-terminal domain of a glycolipid-anchored prion protein is essential for its endocytosis via clathrin-coated pits. J. Biol. Chem. 270, 14793–14800 (1995).

    Article  CAS  Google Scholar 

  13. Gabriel, J.-M., Oesch, B., Kretzschmar, H., Scott, M. & Prusiner, S.B. Molecular cloning of a candidate for chicken prion protein. Proc. Natl. Acad. Sci USA 89, 9097–9101 (1992).

    Article  CAS  Google Scholar 

  14. Brentani, R.R. Biological implications of complementary hydropathy of amino acids. J. Theor. Biol. 135, 495–499 (1988).

    Article  CAS  Google Scholar 

  15. Brentani, R.R. Complementary hydropathy and the evolution of interacting polypeptides. J. Mol. Evol. 31, 239–243 (1990).

    Article  CAS  Google Scholar 

  16. Baranyi, L. et al. The antisense homology box: A new motif within proteins that encodes biologically active peptides. Nature Med. 1, 894–901 (1995).

    Article  CAS  Google Scholar 

  17. Pasqualini, R., Chamone, D.F. & Brentani, R.R. Determination of the putative binding site for fibronectin on platelet glycoprotein llb-llla complex through a hydropathic complementary. J. Biol. Chem. 264, 14566–14570 (1989).

    CAS  PubMed  Google Scholar 

  18. Brentani, R.R. et al. Characterization of the cellular receptor for fibronectin through a hydropathic complementary approach. Proc. Natl. Acad. Sci USA 85, 364–367 (1988).

    Article  CAS  Google Scholar 

  19. Souza, S.J. & Brentani, R.R. Collagen binding site in collagenase can be determined using the concept of sense-antisense peptide interactions. J. Biol. Chem. 267, 13763–13767 (1992).

    PubMed  Google Scholar 

  20. Serban, D., Taraboulos, A., DeArmond, S.J. & Prusiner, S.B. Rapid detection of Creutzfeld-Jacob disease and scrapie prion proteins. Neurology 40, 110–177 (1990).

    Article  CAS  Google Scholar 

  21. Goldgaber, D. Anticipating an anti-prion protein. Nature 351, 106 (1991).

    Article  CAS  Google Scholar 

  22. Harris, D.A. et al. Processing of a cellular prion protein: Identification of N and C-terminal cleavage sites. Biochemistry 32, 1009–1016 (1993).

    Article  CAS  Google Scholar 

  23. Oesch, B. Characterization of the PrP binding proteins. Phil. Tram. R. Soc. Land. B. 343, 443–445 (1994).

    Article  CAS  Google Scholar 

  24. Gasset, M. et al. Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid. Proc. Natl. Acad. Sci USA 89, 10940–10944 (1992).

    Article  CAS  Google Scholar 

  25. Askanas, V., Bilak, M., Engel, W.K., Leclec, A. & Tome, F. Prion protein is strongly immunolocalized at the postsynaptic domain of the human neuromuscular junctions. Neurosci Lett. 159 (1–2), 111–114 (1993).

    Article  CAS  Google Scholar 

  26. Shyng, S.-L., Lehmann, S., Moulder, K.L. & Harris, D.A. Sulfated glycans stimulate endocytosis of the cellular isoform of the prion protein, PrPc, in cultured cells. J. Biol. Chem. 270, 30221–30229 (1995).

    Article  CAS  Google Scholar 

  27. Moura Neto, V., Mallat, M., Jeantet, C. & Prochiantz, A. Microheterogenity of tubulin proteins in neuronal and glial cells from the mouse brain in culture. EMBO J. 2, 1243–1248 (1983).

    Article  CAS  Google Scholar 

  28. Garcia-Abreu, J., Moura Neto, V., Carvalho, S.L. & Cavalcante, L.A.J. Regionally specific properties of midbrain glia. I. interactions with midbrain neurons. Neurosci Res. 40, 471–477 (1995).

    Article  CAS  Google Scholar 

  29. Halfter, W., Reinhard, E., Liverani, D., Ortman, R. & Monard, D. Immunocytochemical localization of glia-derived nexin, laminin and fibronectin on the surface of extracellular matrix of C6 rat glioma cells. Eur. J. Neurosci. 1, 297–308 (1989).

    Article  Google Scholar 

  30. Arvan, P., Cameron, R.S. & Castle, D. Secretory membranes of the rat parotid gland: Preparation and comparative characterization. Methods Enzymol. 98, 75–87 (1983).

    Article  CAS  Google Scholar 

  31. Smith, D.B. & Johnson, K.S. Single-step purification of polypeptides expressed in Escherichia coli as fusion with glutathione S-transferase. Gene 67, 31–40 (1988).

    Article  CAS  Google Scholar 

  32. Weiss, S. et al. Overexpression of active Syrian golden hamster prion protein PrPc as a glutathione S-transferase fusion in heterologous systems. J. Virol. 69, 4776–4783 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Vilma R. Martins and Edgard Graner: These authors contributed equally to this work.

Authors and Affiliations

  1. Fundação Antônio Prudente, Rua Prof. Antônio Prudente, 109/4A, 01509-010, São Paulo, SP, Brazil

    Vilma R. Martins & Silvio M. Zanata

  2. Ludwig Institute for Cancer Research, Rua Prof. Antônio Prudente, 109/4A, 01509-010, São Paulo, SP, Brazil

    Edgard Graner, Sandro J. De Souza, Adriana F. Mercadante, Silvio S. Veiga & Ricardo R. Brentani

  3. Instituto de Ciências Biomédicas, Departamento de Anatomia, Centra de Ciências da Saúde, Bloco F, Ilha do Fundão, UFRJ 21949-900, Rio de Janeiro, Brazil

    José Garcia-Abreu & Vivaldo Moura Neto

  4. Biological Laboratories, Harvard University, Cambridge, Massachusetts, 02138, USA

    Sandro J. De Souza

Authors
  1. Vilma R. Martins
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  2. Edgard Graner
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Martins, V., Graner, E., Garcia-Abreu, J. et al. Complementary hydropathy identifies a cellular prion protein receptor. Nat Med 3, 1376–1382 (1997). https://doi.org/10.1038/nm1297-1376

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