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Prion Protein Genes: Evolutionary and Functional Aspects

  • Chapter
Transmissible Spongiform Encephalopathies:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 172))

Abstract

Over the past decade, a wealth of new information about the biological and physical properties as well as genetics of the particle causing scrapie has accumulated. A host-encoded protein denominated prion protein (PrP) is transformed upon infection into a scrapie-specific isoform (PrPSc). Considerable evidence argues that PrPSc is a major and necessary component of the infectious scrapie particle termed prion (Prusiner 1982; Oesch et al. 1985; Gabizon et al. 1988; Gabizon and Prusiner 1990). Genetically, the PrP gene has been linked to a gene controlling the incubation time and species specificity (Carlson et al. 1986, 1988; Hunter et al. 1987; Mohri and Tateishi 1989; Scott et al. 1989; Race et al. 1990). Unfortunately, we still lack molecular probes directed towards the scrapie-specific portion of prions. The only convenient markers known to date are the protease resistance and detergent insolubility of PrPSc. The identification of different scrapie “strains” or isolates which appear to breed true in the same inbred host suggests that inheritable information independent of the host must be encoded within the infectious particle (Bruce and Dickinson 1987; Kimberlin et al. 1987). This hypothetical informational molecule has been equated with a nucleic acid genome which, however, is still elusive (Alper et al. 1967; Rohwer 1984; Duguid et al. 1988; Oesch et al. 1988; Aiken et al. 1989). As an unusual possibility, inheritable information may be encoded in molecules other than nucleic acid.

This work was supported by research grants from the National Institutes of Health (AG02132 and NS14069) and by a Senator Jacob Javits Center of Excellence in Neuroscience award (NS22786) as well as by a gift from the Sherman Fairchild Foundation. B. Oesch was supported by a postdoctoral fellowship from the European Molecular Biology Organization (EMBO)

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References

  • Aiken JM, Williamson JL, Marsh RF (1989) Evidence of mitochondrial involvement in scrapie infection. J Virol 63: 1686–1694

    PubMed  CAS  Google Scholar 

  • Alper T, Cramp WA, Haig DA, Clarke MC (1967) Does the agent of scrapie replicate without nucleic acid? Nature 214: 764–766

    Article  PubMed  CAS  Google Scholar 

  • Basier K, Oesch B, Scott M, Westaway D, Wälchli M, Groth DF, McKinley MP, Prusiner SB, Weissmann C (1986) Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46: 417–428

    Article  Google Scholar 

  • Bazan JF, Fletterick RJ, McKinley MP, Prusiner SB (1987) Predicted, secondary structure and membrane topology of the scrapie prion protein. Protein Eng 1: 125–135

    Article  PubMed  CAS  Google Scholar 

  • Berger J, Howard AD, Brink L, Gerber L, Hauber J, Cullen BR, Udenfriend S (1988) COOH-terminal requirements for the correct processing of a phosphatidylinositol-glycan anchored membrane protein. J Biol Chem 263: 10016–10021

    PubMed  CAS  Google Scholar 

  • Bolton DC, McKinley MP, Prusiner SB (1982) Identification of a protein that purifies with the scrapie prion. Science 218: 1309–1311

    Article  PubMed  CAS  Google Scholar 

  • Borchelt DR, Scott M, Taraboulos A, Stahl N, Prusiner SB (1990) Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J Cell Biol 110: 743–752

    Article  PubMed  CAS  Google Scholar 

  • Bruce ME, Dickinson AG (1987) Biological evidence that the scrapie agent has an independent genome. J Gen Virol 68: 79–89

    Article  PubMed  Google Scholar 

  • Caras IW, Weddell GN, Williams SR (1989) Analysis of the signal for attachment of a glycophospholipid membrane anchor. J Cell Biol 108: 1387–1396

    Article  PubMed  CAS  Google Scholar 

  • Carlson GA, Goodman P, Kingsbury DT, Prusiner SB (1986) Scrapie incubation time and prion protein genes are linked. Clin Res 34: 675A

    Google Scholar 

  • Carlson GA, Goodman PA, Lovett M, Taylor BA, Marshall ST, Peterson-Torchia M, Westaway D, Prusiner SB (1988) Genetics and polymorphism of the mouse prion gene complex: the control of scrapie incubation time. Mol Cell Biol 8: 5528–5540

    PubMed  CAS  Google Scholar 

  • Cashman NR, Loertscher R, Nalbantoglu J, Shaw I, Kascsak RJ, Bolton DC, Bendheim PE (1990) Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell 61: 185–192

    Article  PubMed  CAS  Google Scholar 

  • Chesebro B, Race R, Wehrly K, Nishio J, Bloom M, Lechner D, Bergstrom S, Robbins K, Mayer L, Keith JM, Garon C, Haase A (1985) Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature 315: 331–333

    Article  PubMed  CAS  Google Scholar 

  • Collinge J, Harding AE, Owen F, Poulter M, Lofthouse R, Boughey AM, Shah T, Crow TJ (1989) Diagnosis of Gerstmann-Sträussler syndrome in familial dementia with prion protein gene analysis. Lancet 2: 15–17

    Article  PubMed  CAS  Google Scholar 

  • Dayhoff MO (1978) In: Atlas of protein sequence and structure, Vol 5, suppl 3. National Biochemical Research Foundation, Washington, DC

    Google Scholar 

  • DeArmond SJ, Mobley WC, Demott DL, Barry RA, Beckstead JH, Prusiner SB (1987) Changes in the localization of brain prion proteins during scrapie infection. Neurology 37: 1271–1280

    PubMed  CAS  Google Scholar 

  • Dohura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y (1989) Pro→Leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Sträussler syndrome. Biochem Biophys Res. Commun 163: 974–979

    Article  CAS  Google Scholar 

  • Duguid JR, Rohwer RG, Seed B (1988) Isolation of cDNAs of scrapie-modulated RNAs by subtractive hybridization of a cDNA library. Proc Natl Acad Sci USA 85:5738–5742

    Article  PubMed  CAS  Google Scholar 

  • Feng D-F, Doolittle RF (1987) Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol 25: 351–360

    Article  PubMed  CAS  Google Scholar 

  • Gabizon R, Prusiner SB (1990) Prion liposomes. Biochem. J 266: 1–14

    Google Scholar 

  • Gabizon R, McKinley MP, Groth DF, Prusiner SB (1988) Immunoaffinity purification and neutralization of scrapie prion infectivity. Proc Natl Acad Sci USA 85: 6617–6621

    Article  PubMed  CAS  Google Scholar 

  • Gibbons RA, Hunter GD (1967) Nature of the scrapie agent. Nature 215: 1041–1043

    Article  PubMed  CAS  Google Scholar 

  • Goldman W, Hunter N, Foster JD, Salbaum JM, Beyreuther K, Hope J (1990) Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci USA 87: 2476–2480

    Article  Google Scholar 

  • Goodman M (1976) Protein sequences in phylogeny. In: Molecular evolution. Sinauer Associates, Massachusetts, Ayala FJ (ed), pp 141–153

    Google Scholar 

  • Haraguchi T, Fisher S, Olofsson S, Endo T, Groth D, Tarantino A, Borchelt DR, Teplow D, Hood L, Burlingame A, Lycke E, Kobata A, Prusiner SB (1989) Asparagine-linked glycosylation of the scrapie and cellular prion proteins. Arch Biochem Biophys 274: 1–13

    Article  PubMed  CAS  Google Scholar 

  • Harris DA, Falls DL, Dill-Devor RM, Fischbach GD (1988) Acetylcholine receptor-inducing factor from chicken brain increases the level of mRNA encoding the receptor alpha subunit. Proc Natl Acad Sci USA 85: 1983–1987

    Article  PubMed  CAS  Google Scholar 

  • Harris DA, Falls DL, Walsh W, Fischbach GD (1989) Molecular cloning of an acetylcholine receptor-inducing protein. Soc Neurosci Abstr 15: 70.7

    Google Scholar 

  • Hay B, Barry RA, Lieberburg I, Prusiner SB, Lingappa VR (1987a) Biogenesis and transmembrane orientation of the cellular isoform of the scrapie prion protein. Mol Cell Biol 7: 914–920

    PubMed  CAS  Google Scholar 

  • Hay B, Prusiner SB, Lingappa VR (1987b) Evidence for a secretory form of the cellular prion protein. Biochemistry 26: 8110–8115

    Article  PubMed  CAS  Google Scholar 

  • Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD, Westaway D, Ott J, Prusiner SB (1989) Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature 338: 342–345

    Article  PubMed  CAS  Google Scholar 

  • Hsiao KK, Cass C, Schellenberg GD, Devine-Gage E, Wisniewski H, Prusiner SB (1991) A prion protein variant in a family with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome. Neurology 41: 681–684

    PubMed  CAS  Google Scholar 

  • Hunter N, Hope J, McConnell I, Dickinson AG (1987) Linkage of the scrapie-associated fibril protein (PrP) gene and Sinc using congenie mice and restriction fragment length polymorphism analysis. J Gen Virol 68: 2711–2716

    Article  PubMed  CAS  Google Scholar 

  • Hunziker W, Spiess M, Semenza G, Lodish HF (1986) The sucrase-isomaltase complex: primary structure, membrane-orientation, and evolution of a stalked, intrinsic brush border protein. Cell 46: 227–234

    Article  PubMed  CAS  Google Scholar 

  • Johnson D, Lanahan A, Buck CR, Sehgal A, Morgan C, Mercer E, Bothwell M, Chao M (1986) Expression and structure of the human NGF receptor. Cell 47: 545–554

    Article  PubMed  CAS  Google Scholar 

  • Kimberlin RH, Cole S, Walker CA (1987) Temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters. J Gen Virol 68: 1875–1881

    Article  PubMed  Google Scholar 

  • Kretzschmar HA, Prusiner SB, Stowring LE, DeArmond SJ (1986a) Scrapie prion proteins are synthesized in neurons. Am J Pathol 122: 1–5

    PubMed  CAS  Google Scholar 

  • Kretzschmar HA, Stowring LE, Westaway D, Stubblebine WH, Prusiner SB, DeArmond SJ (1986b) Molecular cloning of a human prion protein cDNA. DNA 5: 315–324

    Article  PubMed  CAS  Google Scholar 

  • Lee MG, Nurse P (1987) Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327: 31–35

    Article  PubMed  CAS  Google Scholar 

  • Liao Y-C, Lebo RV, Clawson GA, Smuckler EA (1986) Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implication. Science 233: 364–367

    Article  PubMed  CAS  Google Scholar 

  • Liao Y-C, Tokes Z, Lim E, Lackey A, Woo CH, Button JD, Clawson GA (1987) Cloning of rat “prion-related protein” cDNA. Lab Invest 57: 370–374

    PubMed  CAS  Google Scholar 

  • Locht C, Chesebro B, Race R, Keith JM (1986) Molecular cloning and complete sequence of prion protein cDNA from mouse brain infected with the scrapie agent. Proc Natl Acad Sci USA 83: 6372–6376

    Article  PubMed  CAS  Google Scholar 

  • Lopez CD, Yost CS, Prusiner SB, Myers RM, Lingappa VR (1990) Unusual topogenic sequence directs prion protein biogenesis. Science 248: 226–229

    Article  PubMed  CAS  Google Scholar 

  • Lowenstein DH, Butler DA, Westaway D, McKinley MP, DeArmond SJ, Prusiner SB (1990) Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins. Mol Cell Biol 10: 1153–1163

    PubMed  CAS  Google Scholar 

  • Marchuk D, McCrohon S, Fuchs E (1984) Remarkable conservation of structure among intermediate filament genes. Cell 39: 491–498

    Article  PubMed  CAS  Google Scholar 

  • McKinley MP, Bolton DC, Prusiner SB (1983) A protease-resistant protein is a structural component of the scrapie prion. Cell 35: 57–62

    Article  PubMed  CAS  Google Scholar 

  • McKinley MP, Meyer RK, Kenaga L, Rahbar F, Cotter R, Serban A, Prusiner SB (1991) Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis. J Virol 65: 1340–1351

    PubMed  CAS  Google Scholar 

  • Meyer RK, McKinley MP, Bowman KA, Braunfeld MB, Barry RA, Prusiner SB (1986) Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci USA 83: 2310–2314

    Article  PubMed  CAS  Google Scholar 

  • Miyata T, Hayashida H (1982) Recent divergence from a common ancestor of human IFN-α genes. Nature 295: 165–168

    Article  PubMed  CAS  Google Scholar 

  • Mohri S, Tateishi J (1989) Host genetic control of incubation periods of Creutzfeldt-Jakob disease in mice. J Gen Virol 70: 1391–1400

    Article  PubMed  Google Scholar 

  • Oesch B, Westaway D, Wälchli M, McKinley MP, Kent SBH, Aebersold R, Barry RA, Tempst P, Teplow DB, Hood LE, Prusiner SB, Weissmann C (1985) A cellular gene encodes scrapie PrP 27–30 protein. Cell 40: 735–746

    Article  PubMed  CAS  Google Scholar 

  • Oesch B, Groth DF, Prusiner SB, Weissmann C (1988) Search for a scrapie-specific nucleic acid: a progress report. Ciba Found Symp 135

    Google Scholar 

  • Owen F, Poulter M, Lofthouse R, Collinge J, Crow TJ, Risby D, Baker HF, Ridley RM, Hsiao K, Prusiner SB (1989) Insertion in prion protein gene in familial Creutzfeldt-Jakob disease. Lancet 1: 51–52

    Article  PubMed  CAS  Google Scholar 

  • Perler F, Efstratiadis A, Lomedico P, Gilbert W, Kolodner R, Dodgson J (1980) The evolution of genes: the chicken preproinsulin gene. Cell 20: 555–566

    Article  PubMed  CAS  Google Scholar 

  • Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216: 136–144

    Article  PubMed  CAS  Google Scholar 

  • Prusiner SB (1984) Prions. Sci Am 251: 50–59

    Article  PubMed  CAS  Google Scholar 

  • Prusiner SB, Bolton DC, Groth DF, Bowman KA, Cochran SP, Mckinley MP (1982) Further purification and characterization of scrapie prions. Biochemistry 21: 6942–6950

    Article  PubMed  CAS  Google Scholar 

  • Prusiner SB, McKinley MP, Bowman KA, Bolton DC, Bendheim PE, Groth DF, Glenner GG (1983) Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 35: 349–358

    Article  PubMed  CAS  Google Scholar 

  • Prusiner SB, Groth DF, Bolton DC, Kent SB, Hood LE (1984) Purification and structural studies of a major scrapie prion protein. Cell 38: 127–134

    Article  PubMed  CAS  Google Scholar 

  • Race RE, Graham K, Ernst D. Caughey B, Chesebro (1990) Analysis of linkage between scrapie incubation period and the prion protein gene in mice. J Gen Virol 71: 493–497

    Article  PubMed  CAS  Google Scholar 

  • Robakis NK, Sawh PR, Wolfe GC, Rubenstein R, Carp RI, Innis MA (1986) Isolation of a.cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues: Proc Natl Acad Sci USA 83: 6377–6381

    Article  PubMed  CAS  Google Scholar 

  • Rohwer RG (1984) Scrapie infectious agent is virus-like in size and susceptibility to inactivation. Nature 308: 658–662

    Article  PubMed  CAS  Google Scholar 

  • Scott M. Foster D, Mirenda C, Serban D, Coufal F, Wälchli M, Torchia M, Groth D, Carlson G, DeArmond SJ, Westaway D, Prusiner SB (1988) Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques. Cell 59: 847–857

    Article  Google Scholar 

  • Shinagawa M, Munekata E, Doi S, Takahashi K, Goto H, Sato G (1986) Immunoreactivity of a synthetic pentadecapeptide corresponding to the N-terminal region of the scrapie prion protein. J Gen Virol 67: 1745–1750

    Article  PubMed  CAS  Google Scholar 

  • Stahl N, Borchelt DR, Hsiao K, Prusiner SB (1987) Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 51: 229–240

    Article  PubMed  CAS  Google Scholar 

  • Stahl N, Borchelt DR, Prusiner SB (1990) Differential release of cellular and scrapie prion proteins from cellular membranes by phosphatidylinositol-specific phospholipase C. Biochemistry 29: 5405–5412

    Article  PubMed  CAS  Google Scholar 

  • Taraboulos A, Rogers M, Borchelt DR, McKinley MP, Scott M, Serban D, Prusiner SB (1990) Acquisition of protease resistance by prion proteins in scrapie-infected cells does not require asparagine-linked glycosylation. Proc Natl Acad Sci USA 87: 8262–8266

    Article  PubMed  CAS  Google Scholar 

  • Tomita M, Marchesi VT (1975) Amino-acid sequence and oligosaccharide attachment sites of human erythrocyte glycophorin. Proc Natl Acad Sci USA 72: 2964–2968

    Article  PubMed  CAS  Google Scholar 

  • Usdin TB, Fischbach GD (1986) Purification and characterization of a polypeptide from chick brain that promotes the accumulation of acetylcholine receptors in chick myotubes. J Cell Biol 103: 493–507

    Article  PubMed  CAS  Google Scholar 

  • von Heijne G (1985) Signal sequences, the limits of variation. J Mol Biol 184: 99–105

    Article  Google Scholar 

  • Weissmann C, Weber H (1986) The interferon genes. Prog Nucleic Acid Res Mol Bio 33: 251–300

    Article  CAS  Google Scholar 

  • Westaway D, Prusiner SB (1986) Conservation of the cellular gene encoding the scrapie prion protein. Nucleic Acids Res 14: 2035–2044

    Article  PubMed  CAS  Google Scholar 

  • Westaway D, Goodman PA, Mirenda CA, McKinley MP, Carlson GA, Prusiner SB (1987) Distinct prion proteins in short and long scrapie incubation period mice. Cell 51: 651–662

    Article  PubMed  CAS  Google Scholar 

  • Westaway D, Mirenda C, Foster D, Carlson G, Hoppe P, Scott M, Wälchli M, Prusiner S (1990) Molecular genetics of the mouse prion gene complex. Neurobiol Aging 11(1): 86–87

    Google Scholar 

  • Wills PR (1989) Induced frameshifting mechanism of replication for an information-carrying scrapie prion. Microb Pathogen 6: 235–249

    Article  CAS  Google Scholar 

  • Wood WI, Gitschier J, Lasky LA, Lawn RM (1985) Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries. Proc Natl Acad Sci USA 82: 1585–1588

    Article  PubMed  CAS  Google Scholar 

  • Yost CS, Lopez CD, Prusiner SB, Meyers RM, Lingappa VR (1990) A non-hydrophobic extra-cytoplasmic determinant of stop transfer in the prion protein. Nature 343: 669–672

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Neurology, University of California, San Francisco, CA, 94143, USA

    B. Oesch, D. Westaway & S. B. Prusiner

  2. Departments of Biochemistry and Biophysics, University of California, San Francisco, CA, 94143, USA

    S. B. Prusiner

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  1. B. Oesch
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  2. D. Westaway
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  3. S. B. Prusiner
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Editors and Affiliations

  1. Laboratory of Persistent Viral Diseases Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, 59840, USA

    Bruce W. Chesebro M.D. (Chief) (Chief)

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Oesch, B., Westaway, D., Prusiner, S.B. (1991). Prion Protein Genes: Evolutionary and Functional Aspects. In: Chesebro, B.W. (eds) Transmissible Spongiform Encephalopathies:. Current Topics in Microbiology and Immunology, vol 172. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76540-7_7

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