Abstract
Protein misfolding is associated with many neurodegenerative diseases, including neurodegenerative diseases caused by polyglutamine expansion proteins, such as Huntington’s disease. The model organism baker’s yeast (Saccharomyces cerevisiae) has provided important general insights into the basic cellular mechanisms underlying protein misfolding. Furthermore, experiments in yeast have identified cellular factors that modulate the toxicity and the aggregation associated with polyglutamine expansion proteins. Notably, many features discovered in yeast have been proven to be highly relevant in other model organisms and in human pathology. The experimental protocols depicted here serve to reliably determine polyglutamine toxicity and polyglutamine aggregation in yeast.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Soto C (2003) Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 4(1):49–60. doi:10.1038/nrn1007 nrn1007 [pii]
Soto C, Estrada LD (2008) Protein misfolding and neurodegeneration. Arch Neurol 65(2):184–189. doi:65/2/184 [pii] 10.1001/archneurol.2007.56
Duennwald ML, Jagadish S, Giorgini F, Muchowski PJ, Lindquist S (2006) A network of protein interactions determines polyglutamine toxicity. Proc Natl Acad Sci USA 103(29):11051–11056. doi:0604548103 [pii] 10.1073/pnas.0604548103
Duennwald ML, Jagadish S, Muchowski PJ, Lindquist S (2006) Flanking sequences profoundly alter polyglutamine toxicity in yeast. Proc Natl Acad Sci USA 103(29):11045–11050. doi:0604547103 [pii] 10.1073/pnas.0604547103
Krobitsch S, Lindquist S (2000) Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins. Proc Natl Acad Sci USA 97(4):1589–1594. doi:97/4/1589 [pii]
Meriin AB, Zhang X, He X, Newnam GP, Chernoff YO, Sherman MY (2002) Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1. J Cell Biol 157(6):997–1004. doi:10.1083/jcb.200112104 jcb.200112104 [pii]
Muchowski PJ, Schaffar G, Sittler A, Wanker EE, Hayer-Hartl MK, Hartl FU (2000) Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc Natl Acad Sci USA 97(14):7841–7846. doi:10.1073/pnas.140202897 140202897 [pii]
Giorgini F, Muchowski PJ (2009) Exploiting yeast genetics to inform therapeutic strategies for Huntington’s disease. Methods Mol Biol 548:161–174. doi:10.1007/978-1-59745-540-4_9
Sherman MY, Muchowski PJ (2003) Making yeast tremble: yeast models as tools to study neurodegenerative disorders. Neuromolecular Med 4(1–2):133–146. doi:NMM:4:1–2:133 [pii] 10.1385/NMM:4:1–2:133
Winderickx J, Delay C, De Vos A, Klinger H, Pellens K, Vanhelmont T, Van Leuven F, Zabrocki P (2008) Protein folding diseases and neurodegeneration: lessons learned from yeast. Biochim Biophys Acta 1783(7):1381–1395. doi:S0167-4889(08)00046-3 [pii] 10.1016/j.bbamcr.2008.01.020
Shorter J, Lindquist S (2005) Prions as adaptive conduits of memory and inheritance. Nat Rev Genet 6(6):435–450. doi:nrg1616 [pii] 10.1038/nrg1616
Sondheimer N, Lindquist S (2000) Rnq1: an epigenetic modifier of protein function in yeast. Mol Cell 5(1):163–172. doi:S1097-2765(00)80412-8 [pii]
Duennwald ML (2011) Monitoring polyglutamine toxicity in yeast. Methods 53(3):232–237. doi:S1046-2023(10)00284-7 [pii] 10.1016/j.ymeth.2010.12.001
Acknowledgments
Research in the Duennwald lab is supported by grants from the American Federation for Aging Research (AFAR), the Hereditary Disease Foundation (HDF), and the William Wood Foundation.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media, New York
About this protocol
Cite this protocol
Duennwald, M.L. (2013). Yeast as a Platform to Explore Polyglutamine Toxicity and Aggregation. In: Hatters, D., Hannan, A. (eds) Tandem Repeats in Genes, Proteins, and Disease. Methods in Molecular Biology, vol 1017. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-438-8_11
Download citation
DOI: https://doi.org/10.1007/978-1-62703-438-8_11
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-437-1
Online ISBN: 978-1-62703-438-8
eBook Packages: Springer Protocols