Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Development of a Novel Yeast Cell-Based System for Studying the Aggregation of Alzheimer’s Disease-Associated Aβ Peptides in vivo

von der Haar T. · Jossé L. · Wright P. · Zenthon J. · Tuite M.F.

Author affiliations

Protein Science Group, Department of Biosciences, University of Kent, Canterbury, UK

Related Articles for ""

Neurodegenerative Dis 2007;4:136–147

Do you have an account?

Login Information





Contact Information










I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information










I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Paper

Received: August 16, 2006
Accepted: November 28, 2006
Published online: June 29, 2007
Issue release date: June 2007

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 0

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Abstract

Alzheimer’s disease is the most common neurodegenerative disease, affecting ∼50% of humans by age 85. The disease process is associated with aggregation of the Aβ peptides, short 39–43 residue peptides generated through endoproteolytic cleavage of the Alzheimer’s precursor protein. While the process of aggregation of purified Aβ peptides in vitro is beginning to be well understood, little is known about this process in vivo. In the present study, we use the yeast Saccharomyces cerevisiae as a model system for studying Aβ-mediated aggregation in an organism in vivo. One ofthis yeast’s endogenous prions, Sup35/[PSI+], loses the ability to aggregate when the prion-forming domain of this protein is deleted. We show that insertion of Aβ peptide sequences in place of the original prion domain of this protein restores its ability to aggregate. However, the aggregates are qualitatively different from [PSI+] prions in their sensitivity to detergents and in their requirements on trans-acting factors that are normally needed for [PSI+] propagation. We conclude that we have established a useful new tool for studying the aggregation of Aβ peptides in an organism in vivo.

© 2007 S. Karger AG, Basel


References

  1. Gaggelli E, Kozlowski H, Valensin D, Valensin G: Copper homeostasis and neurodegenerative disorders (Alzheimer’s, prion, and Parkinson’s diseases and amyotrophic lateral sclerosis). Chem Rev 2006;106:1995–2044.
  2. 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 1997;94:9773–9778.
  3. Maddelein ML, Dos Reis S, Duvezin-Caubet S, Coulary-Salin B, Saupe SJ: Amyloid aggregates of the HET-s prion protein are infectious. Proc Natl Acad Sci USA 2002;99:7402–7407.
  4. Tuite MF, Cox BS: The [PSI+] prion of yeast: a problem of inheritance. Methods 2006;39:9–22.
  5. Edskes HK: Protein-based inheritance in Saccharomyces cerevisiae: [URE3] as a prion form of the nitrogen regulatory protein Ure2. Res Microbiol 2001;152:605–612.
  6. Derkatch IL, Bradley ME, Hong JY, Liebman SW: Prions affect the appearance of other prions: the story of [PIN+]. Cell 2001;106:171–182.
  7. King CY, Diaz-Avalos R: Protein-only transmission of three yeast prion strains. Nature 2004;428:319–323.
  8. Tanaka M, Chien P, Naber N, Cooke R, Weissman JS: Conformational variations in an infectious protein determine prion strain differences. Nature 2004;428:323–328.
  9. True HL, Berlin I, Lindquist SL: Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 2004;431:184–187.
  10. King CY, Tittmann P, Gross H, Gebert R, Aebi M, Wuthrich K: Prion-inducing domain 2–114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments. Proc Natl Acad Sci USA 1997;94:6618–6622.
  11. Ter-Avanesyan MD, Dagkesamanskaya AR, Kushnirov VV, Smirnov VN: The SUP35 omnipotent suppressor gene is involved in the maintenance of the non-Mendelian determinant [psi+] in the yeast Saccharomyces cerevisiae. Genetics 1994;137:671–676.
  12. Liu JJ, Sondheimer N, Lindquist SL: Changes in the middle region of Sup35 profoundly alter the nature of epigenetic inheritance for the yeast prion [PSI+]. Proc Natl Acad Sci USA 2002;99(suppl 4):16446–16453.
  13. Hara H, Nakayashiki T, Crist CG, Nakamura Y: Prion domain interaction responsible for species discrimination in yeast [PSI+] transmission. Genes Cells 2003;8:925–939.
  14. Osherovich LZ, Cox BS, Tuite MF, Weissman JS: Dissection and design of yeast prions. PLoS Biol 2004;2:442–451.
  15. Li L, Lindquist S: Creating a protein-based element of inheritance. Science 2000;287:661–664.
  16. Parham SN, Resende CG, Tuite MF: Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion interactions. EMBO J 2001;20:2111–2119.
  17. Chernoff YO, Lindquist SL, Ono B, Inge-Vechtomov SG, Liebman SW: Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science 1995;268:880–884.
  18. Guldener U, Heck S, Fielder T, Beinhauer J, Hegemann JH: A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res 1996;24:2519–2524.
  19. Horton RM, Hunt HD, Ho SN, Pullen JK, Pease LR: Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 1989;77:61–68.
  20. Gietz RD, Woods RA: Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 2002;350:87–96.
  21. Boeke JD, Trueheart J, Natsoulis G, Fink GR: 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol 1987;154:164–175.
  22. Kushnirov VV: Rapid and reliable protein extraction from yeast. Yeast 2000;16:857–860.
  23. Ness F, Ferreira P, Cox BS, Tuite MF: Guanidine hydrochloride inhibits the generation of prion ‘seeds’ but not prion protein aggregation in yeast. Mol Cell Biol 2002;22:5593–5605.
  24. Cox BS, Tuite MF, Mundy CJ: Reversion from suppression to non-suppression in SUQ5 [psi+] strains of yeast: the classification of mutations. Genetics 1980;95:589–609.
  25. Middendorp O, Ortler C, Neumann U, Paganetti P, Luthi U, Barberis A: Yeast growth selection system for the identification of cell-active inhibitors of beta-secretase. Biochim Biophys Acta 2004;1674:29–39.
  26. Greenfield JP, Xu H, Greengard P, Gandy S, Seeger M: Generation of the amyloid-beta peptide N terminus in Saccharomyces cerevisiae expressing human Alzheimer’s amyloid-beta precursor protein. J Biol Chem 1999;274:33843–33846.
  27. Madeo F, Frohlich E, Ligr M, Grey M, Sigrist SJ, Wolf DH, Frohlich KU: Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol 1999;145:757–767.
  28. Schulz JB, Weller M, Klockgether T: Potassium deprivation-induced apoptosis of cerebellar granule neurons: a sequential requirement for new mRNA and protein synthesis, ICE-like protease activity, and reactive oxygen species. J Neurosci 1996;16:4696–4706.
  29. Rospert S, Rakwalska M, Dubaquie Y: Polypeptide chain termination and stop codon readthrough on eukaryotic ribosomes. Rev Physiol Biochem Pharmacol 2005;155:1–30.
  30. Cox BS: A cytoplasmic suppressor of super-suppression in yeast. Heredity 1965;20:505–521.
    External Resources
  31. Patino MM, Liu JJ, Glover JR, Lindquist S: Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science 1996;273:622–626.
  32. Paushkin SV, Kushnirov VV, Smirnov VN, Ter-Avanesyan MD: Propagation of the yeast prion-like [psi+] determinant is mediated by oligomerization of the SUP35-encoded polypeptide chain release factor. EMBO J 1996;15:3127–3134.
  33. Ganusova EE, Ozolins LN, Bhagat S, Newnam GP, Wegrzyn RD, Sherman MY, Chernoff YO: Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast. Mol Cell Biol 2006;26:617–629.
  34. Davis J, Van Nostrand WE: Enhanced pathologic properties of Dutch-type mutant amyloid beta-protein. Proc Natl Acad Sci USA 1996;93:2996–3000.
  35. Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Younkin SG, Naslund J, Lannfelt L: The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Abeta protofibril formation. Nat Neurosci 2001;4:887–893.
  36. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S: Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 1996;2:864–870.
  37. Jarrett JT, Berger EP, Lansbury PT Jr: The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer’s disease. Biochemistry 1993;32:4693–4697.
  38. Liebman SW, Bagriantsev SN, Derkatch IL: Biochemical and genetic methods for characterization of [PIN+] prions in yeast. Methods 2006;39:23–34.
  39. Kryndushkin DS, Alexandrov IM, Ter-Avanesyan MD, Kushnirov VV: Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104. J Biol Chem 2003;278:49636–49643.
  40. Prusiner SB, Groth D, Serban A, Stahl N, Gabizon R: Attempts to restore scrapie prion infectivity after exposure to protein denaturants. Proc Natl Acad Sci USA 1993;90:2793–2797.
  41. Jones GW, Tuite MF: Chaperoning prions: the cellular machinery for propagating an infectious protein? Bioessays 2005;27:823–832.
  42. Ferreira PC, Ness F, Edwards SR, Cox BS, Tuite MF: The elimination of the yeast [PSI+] prion by guanidine hydrochloride is the result of Hsp104 inactivation. Mol Microbiol 2001;40:1357–1369.
  43. Tuite MF, Mundy CR, Cox BS: Agents that cause a high frequency of genetic change from [psi+] to [psi--] in Saccharomyces cerevisiae. Genetics 1981;98:691–711.
  44. Derkatch IL, Uptain SM, Outeiro TF, Krishnan R, Lindquist SL, Liebman SW: 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 2004;101:12934–12939.
  45. Dixon C, Mathias N, Zweig RM, Davis DA, Gross DS: Alpha-synuclein targets the plasma membrane via the secretory pathway and induces toxicity in yeast. Genetics 2005;170:47–59.
  46. Derkatch IL, Chernoff YO, Kushnirov VV, Inge-Vechtomov SG, Liebman SW: Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics 1996;144:1375–1386.
  47. Uptain SM, Sawicki GJ, Caughey B, Lindquist S: Strains of [PSI+] are distinguished by their efficiencies of prion-mediated conformational conversion. EMBO J 2001;20:6236–6245.
  48. Chernoff YO, Derkach IL, Inge-Vechtomov SG: Multicopy SUP35 gene induces de-novo appearance of psi-like factors in the yeast Saccharomyces cerevisiae. Curr Genet 1993;24:268–270.
  49. Eaglestone SS, Ruddock LW, Cox BS, Tuite MF: Guanidine hydrochloride blocks a critical step in the propagation of the prion-like determinant [PSI+] of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 2000;97:240–244.
  50. Hortschansky P, Schroeckh V, Christopeit T, Zandomeneghi G, Fandrich M: The aggregation kinetics of Alzheimer’s beta-amyloid peptide is controlled by stochastic nucleation. Protein Sci 2005;14:1753–1759.
  51. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O’Shea EK, Weissman JS: Global analysis of protein expression in yeast. Nature 2003;425:737–741.
  52. von der Haar T, McCarthy JE: Intracellular translation initiation factor levels in Saccharomyces cerevisiae and their role in cap-complex function. Mol Microbiol 2002;46:531–544.

Article / Publication Details

First-Page Preview
Abstract of Paper

Received: August 16, 2006
Accepted: November 28, 2006
Published online: June 29, 2007
Issue release date: June 2007

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 0

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.