Prions as adaptive conduits of memory and inheritance (original) (raw)

• James, L. C. & Tawfik, D. S. Conformational diversity and protein evolution — a 60-year-old hypothesis revisited. Trends Biochem. Sci. 28, 361–368 (2003).
  Article CAS PubMed Google Scholar
• Prusiner, S. B. Novel proteinaceous infectious particles cause scrapie. Science 216, 136–144 (1982).
  Article CAS PubMed Google Scholar
• Wickner, R. B. [_URE3_] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science 264, 566–569 (1994).
  Article CAS PubMed Google Scholar
• Si, K., Lindquist, S. & Kandel, E. R. A neuronal isoform of the Aplysia CPEB has prion-like properties. Cell 115, 879–891 (2003). This paper shows that ApCPEB can function as a prion in yeast, and that the prion conformation is the most active in stimulating translation of CPEB-regulated mRNA. Together with data from reference 99, the authors propose that the formation of ApCPEB prions in specifically stimulated synapses helps to maintain long-term synaptic changes that are associated with memory storage.
  Article CAS PubMed Google Scholar
• Prusiner, S. B. Prion Biology and Diseases (Cold Spring Harbor Laboratory Press, New York, 2004).
  Google Scholar
• Uptain, S. M. & Lindquist, S. Prions as protein-based genetic elements. Annu. Rev. Microbiol. 56, 703–741 (2002).
  Article CAS PubMed Google Scholar
• Wickner, R. B., Liebman, S. W. & Saupe, S. J. in Prion Biology and Diseases (ed. Prusiner, S. B.) 305–372 (Cold Spring Harbor Laboratory Press New York, 2004).
  Google Scholar
• Chien, P., Weissman, J. S. & DePace, A. H. Emerging principles of conformation-based prion inheritance. Annu. Rev. Biochem. 73, 617–656 (2004).
  Article CAS PubMed Google Scholar
• Alper, T., Cramp, W. A., Haig, D. A. & Clarke, M. C. Does the agent of scrapie replicate without nucleic acid? Nature 214, 764–766 (1967).
  Article CAS PubMed Google Scholar
• Griffith, J. S. Self-replication and scrapie. Nature 215, 1043–1044 (1967).
  Article CAS PubMed Google Scholar
• Prusiner, S. B. et al. Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 35, 349–358 (1983).
  Article CAS PubMed Google Scholar
• Kong, Q. et al. in Prion Biology and Diseases (ed. Prusiner, S. B.) 673–775 (Cold Spring Laboratory Press New York, 2004).
  Google Scholar
• Bueler, H. et al. Mice devoid of PrP are resistant to scrapie. Cell 73, 1339–1347 (1993).
  Article CAS PubMed Google Scholar
• Brandner, S. et al. Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379, 339–343 (1996).
  Article CAS PubMed Google Scholar
• Safar, J. et al. Eight prion strains have PrPSc molecules with different conformations. Nature Med. 4, 1157–1165 (1998).
  Article CAS PubMed Google Scholar
• Cox, B. S. [PSI], a cytoplasmic suppressor of super-suppression in yeast. Heredity 20, 505–521 (1965).
  Article Google Scholar
• Lacroute, F. Non-Mendelian mutation allowing ureidosuccinic acid uptake in yeast. J. Bacteriol. 106, 519–522 (1971).
  CAS PubMed PubMed Central Google Scholar
• Sondheimer, N. & Lindquist, S. Rnq1: an epigenetic modifier of protein function in yeast. Mol. Cell 5, 163–172 (2000).
  Article CAS PubMed Google Scholar
• Santoso, A., Chien, P., Osherovich, L. Z. & Weissman, J. S. Molecular basis of a yeast prion species barrier. Cell 100, 277–288 (2000).
  Article CAS PubMed Google Scholar
• Osherovich, L. Z., Cox, B. S., Tuite, M. F. & Weissman, J. S. Dissection and design of yeast prions. PLoS Biol. 2, E86 (2004).
  Article PubMed PubMed Central Google Scholar
• Coustou, V., Deleu, C., Saupe, S. & Begueret, J. The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog. Proc. Natl Acad. Sci. USA 94, 9773–9778 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Baskakov, I. V., Legname, G., Baldwin, M. A., Prusiner, S. B. & Cohen, F. E. Pathway complexity of prion protein assembly into amyloid. J. Biol. Chem. 277, 21140–21148 (2002).
  Article CAS PubMed Google Scholar
• Glover, J. R. et al. Self-seeded fibres formed by Sup35, the protein determinant of [PSI+], a heritable prion-like factor of S. cerevisiae. Cell 89, 811–819 (1997).
  Article CAS PubMed Google Scholar
• Taylor, K. L., Cheng, N., Williams, R. W., Steven, A. C. & Wickner, R. B. Prion domain initiation of amyloid formation in vitro from native Ure2p. Science 283, 1339–1343 (1999).
  Article CAS PubMed Google Scholar
• Maddelein, M. L., Dos Reis, S., Duvezin-Caubet, S., Coulary-Salin, B. & Saupe, S. J. Amyloid aggregates of the HET-s prion protein are infectious. Proc. Natl Acad. Sci. USA 99, 7402–7407 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Patino, M. M., Liu, J. J., Glover, J. R. & Lindquist, S. Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science 273, 622–626 (1996).
  Article CAS PubMed Google Scholar
• Paushkin, S. V., Kushnirov, V. V., Smirnov, V. N. & Ter-Avanesyan, M. D. Propagation of the yeast prion-like [PSI+] determinant is mediated by oligomerization of the SUP35-encoded polypeptide chain release factor. EMBO J. 15, 3127–3134 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Masison, D. C. & Wickner, R. B. Prion-inducing domain of yeast Ure2p and protease resistance of Ure2p in prion-containing cells. Science 270, 93–95 (1995).
  Article CAS PubMed Google Scholar
• Balguerie, A. et al. Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina. EMBO J. 22, 2071–2081 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Speransky, V. V., Taylor, K. L., Edskes, H. K., Wickner, R. B. & Steven, A. C. Prion filament networks in [_URE3_] cells of Saccharomyces cerevisiae. J. Cell Biol. 153, 1327–1336 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kimura, Y., Koitabashi, S. & Fujita, T. Analysis of yeast prion aggregates with amyloid-staining compound in vivo. Cell Struct. Funct. 28, 187–193 (2003).
  Article CAS PubMed Google Scholar
• Kryndushkin, D. S., Alexandrov, I. M., Ter-Avanesyan, M. D. & Kushnirov, V. V. Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104. J. Biol. Chem. 278, 49636–49643 (2003).
  Article CAS PubMed Google Scholar
• King, C. Y. & Diaz-Avalos, R. Protein-only transmission of three yeast prion strains. Nature 428, 319–323 (2004).
  Article CAS PubMed Google Scholar
• Serio, T. R. et al. Nucleated conformational conversion and the replication of conformational information by a prion determinant. Science 289, 1317–1321 (2000).
  Article CAS PubMed Google Scholar
• Dobson, C. M. Protein folding and misfolding. Nature 426, 884–890 (2003).
  Article CAS PubMed Google Scholar
• Tanaka, M., Chien, P., Naber, N., Cooke, R. & Weissman, J. S. Conformational variations in an infectious protein determine prion strain differences. Nature 428, 323–328 (2004). References 33 and 36 provide definitive evidence for the yeast prion hypothesis. They establish beyond doubt that [ PSI+] is caused by self-replicating conformers of Sup35, and that distinct, stably propagating Sup35 conformations underpin different [ PSI+] variants.
  Article CAS PubMed Google Scholar
• Legname, G. et al. Synthetic mammalian prions. Science 305, 673–676 (2004).
  Article CAS PubMed Google Scholar
• DePace, A. H. & Weissman, J. S. Origins and kinetic consequences of diversity in Sup35 yeast prion fibres. Nature Struct. Biol. 9, 389–396 (2002).
  CAS PubMed Google Scholar
• Baxa, U., Speransky, V., Steven, A. C. & Wickner, R. B. Mechanism of inactivation on prion conversion of the Saccharomyces cerevisiae Ure2 protein. Proc. Natl Acad. Sci. USA 99, 5253–5260 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Fink, G. R. A transforming principle. Cell 120, 153–154 (2005).
  Article CAS PubMed Google Scholar
• Kaneko, K. et al. A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice. J. Mol. Biol. 295, 997–1007 (2000).
  Article CAS PubMed Google Scholar
• Legname, G. et al. Strain-specified characteristics of mouse synthetic prions. Proc. Natl Acad. Sci. USA 102, 2168–2173 (2005). References 37, 41 and 42 provide the initial foundations of definitive evidence for the mammalian prion hypothesis.
  Article CAS PubMed PubMed Central Google Scholar
• Edskes, H. K. & Wickner, R. B. Transmissible spongiform encephalopathies: prion proof in progress. Nature 430, 977–979 (2004).
  Article CAS PubMed Google Scholar
• Goudsmit, J. et al. Evidence for and against the transmissibility of Alzheimer disease. Neurology 30, 945–950 (1980).
  Article CAS PubMed Google Scholar
• West, M. W. et al. De novo amyloid proteins from designed combinatorial libraries. Proc. Natl Acad. Sci. USA 96, 11211–11216 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Medawar, P. B. An Unsolved Problem of Biology (H. K. Lewis, London, 1952).
  Google Scholar
• Chernoff, Y. O. et al. Evolutionary conservation of prion-forming abilities of the yeast Sup35 protein. Mol. Microbiol. 35, 865–876 (2000).
  Article CAS PubMed Google Scholar
• Nakayashiki, T., Ebihara, K., Bannai, H. & Nakamura, Y. Yeast [PSI+] 'prions' that are crosstransmissible and susceptible beyond a species barrier through a quasi-prion state. Mol. Cell 7, 1121–1130 (2001).
  Article CAS PubMed Google Scholar
• Baudin-Baillieu, A., Fernandez-Bellot, E., Reine, F., Coissac, E. & Cullin, C. Conservation of the prion properties of Ure2p through evolution. Mol. Biol. Cell 14, 3449–3458 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Jensen, M. A., True, H. L., Chernoff, Y. O. & Lindquist, S. Molecular population genetics and evolution of a prion-like protein in Saccharomyces cerevisiae. Genetics 159, 527–535 (2001).
  CAS PubMed PubMed Central Google Scholar
• Lindquist, S. Mad cows meet psi-chotic yeast: the expansion of the prion hypothesis. Cell 89, 495–498 (1997).
  Article CAS PubMed Google Scholar
• Berson, J. F. et al. Proprotein convertase cleavage liberates a fibrillogenic fragment of a resident glycoprotein to initiate melanosome biogenesis. J. Cell Biol. 161, 521–533 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Mackay, J. P. et al. The hydrophobin EAS is largely unstructured in solution and functions by forming amyloid-like structures. Structure 9, 83–91 (2001).
  Article CAS PubMed Google Scholar
• Chapman, M. R. et al. Role of Escherichia coli curli operons in directing amyloid fiber formation. Science 295, 851–855 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Kranenburg, O. et al. Tissue-type plasminogen activator is a multiligand cross-β structure receptor. Curr. Biol. 12, 1833–1839 (2002). References 52–55 provide fascinating examples of beneficial amyloid conformers.
  Article CAS PubMed Google Scholar
• Gebbink, M. F., Voest, E. E. & Reijerkerk, A. Do antiangiogenic protein fragments have amyloid properties? Blood 104, 1601–1605 (2004).
  Article CAS PubMed Google Scholar
• Nucifora, F. C. Jr. et al. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 291, 2423–2428 (2001).
  Article CAS PubMed Google Scholar
• Kayed, R. et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300, 486–489 (2003).
  Article CAS PubMed Google Scholar
• Chernoff, Y. O., Lindquist, S. L., Ono, B., Inge-Vechtomov, S. G. & Liebman, S. W. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [PSI+]. Science 268, 880–884 (1995).
  Article CAS PubMed Google Scholar
• Moriyama, H., Edskes, H. K. & Wickner, R. B. [URE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p. Mol. Cell Biol. 20, 8916–8922 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Sondheimer, N., Lopez, N., Craig, E. A. & Lindquist, S. The role of Sis1 in the maintenance of the [RNQ+] prion. EMBO J. 20, 2435–2442 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Lopez, N., Aron, R. & Craig, E. A. Specificity of class II Hsp40 Sis1 in maintenance of yeast prion [RNQ+]. Mol. Biol. Cell. 14, 1172–1181 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Mallucci, G. et al. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 302, 871–874 (2003). This remarkable paper shows that prion diseases might be treated post infection by downregulating endogenous PrP.
  Article CAS PubMed Google Scholar
• Dorn, G. et al. siRNA relieves chronic neuropathic pain. Nucleic Acids Res. 32, e49 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Xia, H. et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nature Med. 10, 816–820 (2004).
  Article PubMed Google Scholar
• Komar, A. A. et al. Internal initiation drives the synthesis of Ure2 protein lacking the prion domain and affects [URE3] propagation in yeast cells. EMBO J. 22, 1199–1209 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• True, H. L. & Lindquist, S. L. A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407, 477–483 (2000).
  Article CAS PubMed Google Scholar
• Uptain, S. M., Sawicki, G. J., Caughey, B. & Lindquist, S. Strains of [PSI+] are distinguished by their efficiencies of prion-mediated conformational conversion. EMBO J. 20, 6236–6245 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Bidou, L. et al. Nonsense-mediated decay mutants do not affect programmed-1 frameshifting. RNA 6, 952–961 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Kellis, M., Patterson, N., Endrizzi, M., Birren, B. & Lander, E. S. Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241–254 (2003).
  Article CAS PubMed Google Scholar
• True, H. L., Berlin, I. & Lindquist, S. L. Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 431, 184–187 (2004). Together with reference 67, this paper makes a compelling case for [ PSI+] as a beneficial prion.
  Article CAS PubMed Google Scholar
• Eaglestone, S. S., Cox, B. S. & Tuite, M. F. Translation termination efficiency can be regulated in Saccharomyces cerevisiae by environmental stress through a prion-mediated mechanism. EMBO J. 18, 1974–1981 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Orr, H. A. The population genetics of adaptation: the distribution of factors fixed during adaptive evolution. Evolution 52, 935–949 (1998).
  Article PubMed Google Scholar
• Partridge, L. & Barton, N. H. Evolving evolvability. Nature 407, 457–458 (2000).
  Article CAS PubMed Google Scholar
• Brookfield, J. F. Evolution: the evolvability enigma. Curr. Biol. 11, R106–R108 (2001).
  Article CAS PubMed Google Scholar
• Kirschner, M. & Gerhart, J. Evolvability. Proc. Natl Acad. Sci. USA 95, 8420–8427 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Masel, J. & Bergman, A. The evolution of the evolvability properties of the yeast prion [PSI+]. Evolution Int. J. Org. Evolution 57, 1498–1512 (2003). A convincing modelling study suggesting that [ PSI+] has probably been maintained owing to the evolvability properties that it confers.
  Article Google Scholar
• Earl, D. J. & Deem, M. W. Evolvability is a selectable trait. Proc. Natl Acad. Sci. USA 101, 11531–11536 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Resende, C. G., Outeiro, T. F., Sands, L., Lindquist, S. & Tuite, M. F. Prion protein gene polymorphisms in Saccharomyces cerevisiae. Mol. Microbiol. 49, 1005–1017 (2003).
  Article CAS PubMed Google Scholar
• Lindquist, S. But yeast prion offers clues about evolution. Nature 408, 17–18 (2000).
  Article CAS PubMed Google Scholar
• Harrison, P. et al. A small reservoir of disabled ORFs in the yeast genome and its implications for the dynamics of proteome evolution. J. Mol. Biol. 316, 409–419 (2002).
  Article CAS PubMed Google Scholar
• Namy, O., Duchateau-Nguyen, G. & Rousset, J. P. Translational readthrough of the PDE2 stop codon modulates cAMP levels in Saccharomyces cerevisiae. Mol. Microbiol. 43, 641–652 (2002).
  Article CAS PubMed Google Scholar
• Dalstra, H. J., Swart, K., Debets, A. J., Saupe, S. J. & Hoekstra, R. F. Sexual transmission of the [Het-s] prion leads to meiotic drive in Podospora anserina. Proc. Natl Acad. Sci. USA 100, 6616–6621 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Derkatch, I. L., Bradley, M. E., Zhou, P., Chernoff, Y. O. & Liebman, S. W. Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae. Genetics 147, 507–519 (1997).
  CAS PubMed PubMed Central Google Scholar
• Derkatch, I. L., Bradley, M. E., Hong, J. Y. & Liebman, S. W. Prions affect the appearance of other prions: the story of [PIN+]. Cell 106, 171–182 (2001).
  Article CAS PubMed Google Scholar
• Bradley, M. E., Edskes, H. K., Hong, J. Y., Wickner, R. B. & Liebman, S. W. Interactions among prions and prion 'strains' in yeast. Proc. Natl Acad. Sci. USA 99 (Suppl. 4), 16392–16399 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Salmon, J. M. & Barre, P. Improvement of nitrogen assimilation and fermentation kinetics under enological conditions by derepression of alternative nitrogen-assimilatory pathways in an industrial Saccharomyces cerevisiae strain. Appl. Environ. Microbiol. 64, 3831–3837 (1998).
  CAS PubMed PubMed Central Google Scholar
• Crespo, J. L., Daicho, K., Ushimaru, T. & Hall, M. N. The GATA transcription factors GLN3 and GAT1 link TOR to salt stress in Saccharomyces cerevisiae. J. Biol. Chem. 276, 34441–34444 (2001).
  Article CAS PubMed Google Scholar
• Bergman, A. & Siegal, M. L. Evolutionary capacitance as a general feature of complex gene networks. Nature 424, 549–552 (2003). This remarkable study indicates that many, if not all, genes expose phenotypic variation when functionally compromised, and that the availability of loss-of-function mutations expedites adaptation to new phenotypic optima. Therefore, evolutionary capacitors might be more widespread than previously anticipated.
  Article CAS PubMed Google Scholar
• Hughes, T. R. et al. Functional discovery via a compendium of expression profiles. Cell 102, 109–126 (2000).
  Article CAS PubMed Google Scholar
• Sangster, T. A., Lindquist, S. & Queitsch, C. Under cover: causes, effects and implications of Hsp90-mediated genetic capacitance. Bioessays 26, 348–362 (2004).
  Article CAS PubMed Google Scholar
• Michelitsch, M. D. & Weissman, J. S. A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. Proc. Natl Acad. Sci. USA 97, 11910–11915 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Harrison, P. M. & Gerstein, M. A method to assess compositional bias in biological sequences and its application to prion-like glutamine/asparagine-rich domains in eukaryotic proteomes. Genome Biol. 4, R40 (2003).
  Article PubMed PubMed Central Google Scholar
• Flechsig, E. et al. Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice. Neuron 27, 399–408 (2000).
  Article CAS PubMed Google Scholar
• Liu, J. J. & Lindquist, S. Oligopeptide-repeat expansions modulate 'protein-only' inheritance in yeast. Nature 400, 573–576 (1999).
  Article CAS PubMed Google Scholar
• Krishnan, R. & Lindquist, S. L. New structural insights on a yeast prion illuminate nucleation and strain diversity. Nature (in the press). This paper defines which regions of the Sup35 prion domain make intermolecular contacts in assembled prion fibres. It also describes how variations in these intermolecular contacts facilitate the construction of different prion variants.
• Ross, E. D., Baxa, U. & Wickner, R. B. Scrambled prion domains form prions and amyloid. Mol. Cell Biol. 24, 7206–7213 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Uversky, V. N. & Fink, A. L. Conformational constraints for amyloid fibrillation: the importance of being unfolded. Biochim. Biophys. Acta 1698, 131–153 (2004).
  Article CAS PubMed Google Scholar
• Si, K. et al. A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia. Cell 115, 893–904 (2003). This paper establishes that neurotransmitter cues upregulate ApCPEB at specific synapses, and that consequent ApCPEB-stimulated translation has a crucial role in the maintenance of synaptic growth associated with long-term facilitation. Together with reference 4, this paper makes a compelling argument that ApCPEB prions function in long-term memory formation.
  Article CAS PubMed Google Scholar
• Bailey, C. H., Kandel, E. R. & Si, K. The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth. Neuron 44, 49–57 (2004).
  Article CAS PubMed Google Scholar
• Lisman, J., Schulman, H. & Cline, H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nature Rev. Neurosci. 3, 175–190 (2002).
  Article CAS Google Scholar
• Bhalla, U. S. & Iyengar, R. Emergent properties of networks of biological signaling pathways. Science 283, 381–387 (1999).
  Article CAS PubMed Google Scholar
• Thayer, M. J. et al. Positive autoregulation of the myogenic determination gene MyoD1. Cell 58, 241–248 (1989).
  Article CAS PubMed Google Scholar
• Way, J. C. & Chalfie, M. The mec-3 gene of Caenorhabditis elegans requires its own product for maintained expression and is expressed in three neuronal cell types. Genes Dev. 3, 1823–1833 (1989).
  Article CAS PubMed Google Scholar
• Mendez, R. & Richter, J. D. Translational control by CPEB: a means to the end. Nature Rev. Mol. Cell Biol. 2, 521–529 (2001).
  Article CAS Google Scholar
• Uversky, V. N., Gillespie, J. R. & Fink, A. L. Why are 'natively unfolded' proteins unstructured under physiologic conditions? Proteins 41, 415–427 (2000).
  Article CAS PubMed Google Scholar
• Sajikumar, S. & Frey, J. U. Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD. Neurobiol. Learn. Mem. 82, 12–25 (2004).
  Article CAS PubMed Google Scholar
• Theis, M., Si, K. & Kandel, E. R. Two previously undescribed members of the mouse CPEB family of genes and their inducible expression in the principal cell layers of the hippocampus. Proc. Natl Acad. Sci. USA 100, 9602–9607 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Li, L. & Lindquist, S. Creating a protein-based element of inheritance. Science 287, 661–664 (2000).
  Article CAS PubMed Google Scholar
• Ter-Avanesyan, M. D. et al. Deletion analysis of the SUP35 gene of the yeast Saccharomyces cerevisiae reveals two non-overlapping functional regions in the encoded protein. Mol. Microbiol. 7, 683–692 (1993).
  Article CAS PubMed Google Scholar
• Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the polycomb and trithorax group proteins. Annu. Rev. Genet. 38, 413–443 (2004).
  Article CAS PubMed Google Scholar
• Kim, C. A., Gingery, M., Pilpa, R. M. & Bowie, J. U. The SAM domain of polyhomeotic forms a helical polymer. Nature Struct. Biol. 9, 453–457 (2002).
  CAS PubMed Google Scholar
• Qiao, F. et al. Derepression by depolymerization; structural insights into the regulation of Yan by Mae. Cell 118, 163–173 (2004).
  Article CAS PubMed Google Scholar
• Roberts, C. W. & Orkin, S. H. The SWI/SNF complex — chromatin and cancer. Nature Rev. Cancer 4, 133–142 (2004).
  Article CAS Google Scholar
• Sudarsanam, P., Iyer, V. R., Brown, P. O. & Winston, F. Whole-genome expression analysis of snf/swi mutants of Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 97, 3364–3369 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Gilks, N. et al. Stress granule assembly is mediated by prion-like aggregation of TIA-1. Mol. Biol. Cell 15, 5383–5398 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Roberts, B. T. & Wickner, R. B. Heritable activity: a prion that propagates by covalent autoactivation. Genes Dev. 17, 2083–2087 (2003).
  Article PubMed PubMed Central Google Scholar
• Collin, P., Beauregard, P. B., Elagoz, A. & Rokeach, L. A. A non-chromosomal factor allows viability of Schizosaccharomyces pombe lacking the essential chaperone calnexin. J. Cell Sci. 117, 907–918 (2004).
  Article CAS PubMed Google Scholar
• Ball, A. J., Wong, D. K. & Elliott, J. J. Glucosamine resistance in yeast. I. A preliminary genetic analysis. Genetics 84, 311–317 (1976).
  CAS PubMed PubMed Central Google Scholar
• Silar, P., Haedens, V., Rossignol, M. & Lalucque, H. Propagation of a novel cytoplasmic, infectious and deleterious determinant is controlled by translational accuracy in Podospora anserina. Genetics 151, 87–95 (1999).
  CAS PubMed PubMed Central Google Scholar
• Talloczy, Z., Menon, S., Neigeborn, L. & Leibowitz, M. J. The [KIL-d] cytoplasmic genetic element of yeast results in epigenetic regulation of viral M double-stranded RNA gene expression. Genetics 150, 21–30 (1998).
  CAS PubMed PubMed Central Google Scholar
• Volkov, K. V. et al. Novel non-Mendelian determinant involved in the control of translation accuracy in Saccharomyces cerevisiae. Genetics 160, 25–36 (2002).
  CAS PubMed PubMed Central Google Scholar
• Derkatch, I. L., Chernoff, Y. O., Kushnirov, V. V., Inge-Vechtomov, S. G. & Liebman, S. W. Genesis and variability of [_PSI_] prion factors in Saccharomyces cerevisiae. Genetics 144, 1375–1386 (1996).
  CAS PubMed PubMed Central Google Scholar
• Ter-Avanesyan, M. D., Dagkesamanskaya, A. R., Kushnirov, V. V. & Smirnov, V. N. The SUP35 omnipotent suppressor gene is involved in the maintenance of the non-Mendelian determinant [PSI+] in the yeast Saccharomyces cerevisiae. Genetics 137, 671–676 (1994).
  CAS PubMed PubMed Central Google Scholar
• Liu, J. J., Sondheimer, N. & Lindquist, S. L. Changes in the middle region of Sup35 profoundly alter the nature of epigenetic inheritance for the yeast prion [PSI+]. Proc. Natl Acad. Sci. USA 99 (Suppl. 4), 16446–16453 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Bagriantsev, S. & Liebman, S. W. Specificity of prion assembly in vivo. [PSI+] and [PIN+] form separate structures in yeast. J. Biol. Chem. 279, 51042–51048 (2004).
  Article CAS PubMed Google Scholar
• Schlumpberger, M., Prusiner, S. B. & Herskowitz, I. Induction of distinct [URE3] yeast prion strains. Mol. Cell Biol. 21, 7035–7046 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Osherovich, L. Z. & Weissman, J. S. Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI+] prion. Cell 106, 183–194 (2001).
  Article CAS PubMed Google Scholar
• Derkatch, I. L. et al. Effects of Q/N-rich, polyQ, and non-polyQ amyloids on the de novo formation of the [PSI+]prion in yeast and aggregation of Sup35 in vitro. Proc. Natl Acad. Sci. USA 101, 12934–12939 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Derkatch, I. L. et al. Dependence and independence of [PSI+] and [PIN+]: a two-prion system in yeast? EMBO J. 19, 1942–1952 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Bradley, M. E. & Liebman, S. W. Destabilizing interactions among [PSI+] and [PIN+] yeast prion variants. Genetics 165, 1675–1685 (2003).
  CAS PubMed PubMed Central Google Scholar
• Baker, H. F., Ridley, R. M., Duchen, L. W., Crow, T. J. & Bruton, C. J. Induction of β(A4)-amyloid in primates by injection of Alzheimer's disease brain homogenate. Comparison with transmission of spongiform encephalopathy. Mol. Neurobiol. 8, 25–39 (1994).
  Article CAS PubMed Google Scholar
• Lundmark, K. et al. Transmissibility of systemic amyloidosis by a prion-like mechanism. Proc. Natl Acad. Sci. USA 99, 6979–6984 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Xing, Y. et al. Induction of protein conformational change in mouse senile amyloidosis. J. Biol. Chem. 277, 33164–33169 (2002).
  Article CAS PubMed Google Scholar
• Prinz, M. et al. Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. Nature 425, 957–962 (2003).
  Article CAS PubMed Google Scholar
• Tanaka, M., Chien, P., Yonekura, K. & Weissman, J. S. Mechanism of cross-species prion transmission; an infectious conformation compatible with two highly divergent yeast prion proteins. Cell 121, 49–62 (2005).
  Article CAS PubMed Google Scholar
• Shorter, J. & Lindquist, S. Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science 304, 1793–1797 (2004). A delineation of how Hsp104 directly regulates Sup35 prion conformers.
  Article CAS PubMed Google Scholar
• Scheibel, T. et al. Conducting nanowires built by controlled self-assembly of amyloid fibres and selective metal deposition. Proc. Natl Acad. Sci. USA 100, 4527–4532 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Masel, J., Jansen, V. A. & Nowak, M. A. Quantifying the kinetic parameters of prion replication. Biophys. Chem. 77, 139–152 (1999).
  Article CAS PubMed Google Scholar
• Lee, D. H., Granja, J. R., Martinez, J. A., Severin, K. & Ghadiri, M. R. A self-replicating peptide. Nature 382, 525–528 (1996).
  Article CAS PubMed Google Scholar
• Lee, D. H., Severin, K., Yokobayashi, Y. & Ghadiri, M. R. Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390, 591–594 (1997).
  Article CAS PubMed Google Scholar
• Saghatelian, A., Yokobayashi, Y., Soltani, K. & Ghadiri, M. R. A chiroselective peptide replicator. Nature 409, 797–801 (2001). References 140–142 describe a remarkable set of short α -helical peptides that can undergo chemical and conformational replication, and which might even help to explain the origins of homochirality.
  Google Scholar
• Pan, K. M. et al. Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc. Natl Acad. Sci. USA 90, 10962–10966 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Wille, H., Zhang, G. F., Baldwin, M. A., Cohen, F. E. & Prusiner, S. B. Separation of scrapie prion infectivity from PrP amyloid polymers. J. Mol. Biol. 259, 608–621 (1996).
  Article CAS PubMed Google Scholar
• Parsell, D. A., Kowal, A. S., Singer, M. A. & Lindquist, S. Protein disaggregation mediated by heat-shock protein Hsp104. Nature 372, 475–478 (1994).
  Article CAS PubMed Google Scholar
• Glover, J. R. & Lindquist, S. Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94, 73–82 (1998).
  Article CAS PubMed Google Scholar
• Wegrzyn, R. D., Bapat, K., Newnam, G. P., Zink, A. D. & Chernoff, Y. O. Mechanism of prion loss after Hsp104 inactivation in yeast. Mol. Cell Biol. 21, 4656–4669 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hattendorf, D. A. & Lindquist, S. L. Analysis of the AAA sensor-2 motif in the C-terminal ATPase domain of Hsp104 with a site-specific fluorescent probe of nucleotide binding. Proc. Natl Acad. Sci. USA 99, 2732–2737 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Hattendorf, D. A. & Lindquist, S. L. Cooperative kinetics of both Hsp104 ATPase domains and interdomain communication revealed by AAA sensor-1 mutants. EMBO J. 21, 12–21 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Grimminger, V., Richter, K., Imhof, A., Buchner, J. & Walter, S. The prion curing agent guanidinium chloride specifically inhibits ATP hydrolysis by Hsp104. J. Biol. Chem. 279, 7378–7383 (2004).
  Article CAS PubMed Google Scholar
• Ripaud, L., Maillet, L. & Cullin, C. The mechanisms of [_URE3_] prion elimination demonstrate that large aggregates of Ure2p are dead-end products. EMBO J. 22, 5251–5259 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Collins, S. R., Douglass, A., Vale, R. D. & Weissman, J. S. Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLoS Biol. 2, e321 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Inoue, Y., Taguchi, H., Kishimoto, A. & Yoshida, M. Hsp104 binds to yeast Sup35 prion fibre but needs other factor(s) to sever it. J. Biol. Chem. 279, 52319–52323 (2004).
  Article CAS PubMed Google Scholar
• Ferreira, P. C., Ness, F., Edwards, S. R., Cox, B. S. & Tuite, M. F. The elimination of the yeast [PSI+] prion by guanidine hydrochloride is the result of Hsp104 inactivation. Mol. Microbiol. 40, 1357–1369 (2001).
  Article CAS PubMed Google Scholar
• Shorter, J. & Lindquist, S. Navigating the ClpB channel to solution. Nature Struct. Mol. Biol. 12, 4–6 (2005).
  Article CAS Google Scholar
• Serio T. R. & Lindquist S. L. Protein-only inheritance in yeast: something to get [PSI+]-ched about. Trends Cell Biol. 10, 98–105 (2000).
  Article CAS PubMed Google Scholar
• Leeds, P., Peltz, S. W., Jacobson, A. & Culbertson, M. R. The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Genes Dev. 5, 2303–2314 (1991).
  Article CAS PubMed Google Scholar
• Frischmeyer, P. A. et al. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science 295, 2258–2261 (2002).
  Article CAS PubMed Google Scholar
• Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292, 1552–155 (2001).
  Article CAS PubMed Google Scholar
• Venkatraman, P., Wetzel, R., Tanaka, M., Nukina, N. & Goldberg, A. L. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell 14, 95–104 (2004).
  Article CAS PubMed Google Scholar
• Castilla, J., Saa, P., Hetz, C. & Soto, C. In vitro generation of infectious scrapie prions. Cell 121, 195–206 (2005).
  Article CAS PubMed Google Scholar
• Zou, W. Q. & Gambetti, P. From microbes to prions the final proof of the prion hypothesis. Cell 121, 155–157 (2005).
  Article CAS PubMed Google Scholar