Yeast Short-Lived Actin-Associated Protein Forms a Metastable Prion in Response to Thermal Stress

• Type of Material: Article
• Authors: Tatiana Chernova, Emory University; Denis A. Kiktev, Georgia Institute of Technology; Andrey V. Romanyuk, Georgia Institute of Technology; John R. Shanks, Emory University School of Medicine; Oskar Laur, Emory University; Moiez Ali, Emory University; Abheek Ghosh, Emory University; Dami Kim, Emory University; Zhen Yang, Emory University; Maggie Mang, Emory University; Yury O. Chernoff, Georgia Institute of Technology; Keith Wilkinson, Emory University
• Language: English
• Date: 2017-01-17
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author(s).
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2016.12.082
• Title of Journal or Parent Work: Cell Reports
• ISSN: 2211-1247
• Volume: 18
• Issue: 3
• Start Page: 751
• End Page: 761
• Grant/Funding Information: M.A. was supported by SURE and M.M were supported by SURE and SIRE grant.; This study was supported by grant GM093294 from National Institutes of Health to KDW, and MCB 1516872 from National Science Foundation to YOC.; In addition, work performed by DAK and YOC at St. Petersburg State University (SPbSU) was supported by the SPbSU project 15.61.2218.2013 and grant 14-50-00069 from Russian Science Foundation.
• Keywords: amyloids; chaperone; actin; Sup35; heat shock; environmental stress; ubiquitination; prions
• Research Categories: Chemistry, Biochemistry; Biology, Microbiology

Abstract

Self-perpetuating ordered protein aggregates (amyloids and prions) are associated with a variety of neurodegenerative disorders. Although environmental agents have been linked to certain amyloid diseases, the molecular basis of their action remains unclear. We have employed endogenous yeast prions as a model system to study environmental control of amyloid formation. A short-lived actin-associated yeast protein Lsb2 can trigger prion formation by other proteins in a mode regulated by the cytoskeleton and ubiquitin-dependent processes. Here, we show that such a heterologous prion induction is due to the ability of Lsb2 to form a transient prion state, generated in response to thermal stress. Evolutionary acquisition of prion-inducing activity by Lsb2 is traced to a single amino acid change, coinciding with the acquisition of thermotolerance in the Saccharomyces yeast lineage. This raises the intriguing possibility that the transient prion formation could aid in functioning of Lsb2 at higher temperatures.