| Title: | Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association |
| Author(s): | Chernova TA; Yang Z; Karpova TS; Shanks JR; Shcherbik N; Wilkinson KD; Chernoff YO; |
| Address: | "Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. Center for Cancer Research Core Fluorescence Imaging Facility, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Department of Cell Biology, Rowan University, School of Osteopathic Medicine, Stratford, NJ 08084, USA. School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332-2000, USA. Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia" |
| ISSN/ISBN: | 1422-0067 (Electronic) 1422-0067 (Linking) |
| Abstract: | "Yeast prions and mnemons are respectively transmissible and non-transmissible self-perpetuating protein assemblies, frequently based on cross-beta ordered detergent-resistant aggregates (amyloids). Prions cause devastating diseases in mammals and control heritable traits in yeast. It was shown that the de novo formation of the prion form [PSI(+)] of yeast release factor Sup35 is facilitated by aggregates of other proteins. Here we explore the mechanism of the promotion of [PSI(+)] formation by Ste18, an evolutionarily conserved gamma subunit of a G-protein coupled receptor, a key player in responses to extracellular stimuli. Ste18 forms detergent-resistant aggregates, some of which are colocalized with de novo generated Sup35 aggregates. Membrane association of Ste18 is required for both Ste18 aggregation and [PSI(+)] induction, while functional interactions involved in signal transduction are not essential for these processes. This emphasizes the significance of a specific location for the nucleation of protein aggregation. In contrast to typical prions, Ste18 aggregates do not show a pattern of heritability. Our finding that Ste18 levels are regulated by the ubiquitin-proteasome system, in conjunction with the previously reported increase in Ste18 levels upon the exposure to mating pheromone, suggests that the concentration-dependent Ste18 aggregation may mediate a mnemon-like response to physiological stimuli" |
| Keywords: | Cell Membrane/metabolism GTP-Binding Protein gamma Subunits/analysis/*metabolism Peptide Termination Factors/analysis/*metabolism *Protein Aggregates Proteolysis Saccharomyces cerevisiae/*metabolism/ultrastructure Saccharomyces cerevisiae Proteins/analysi; |
| Notes: | "MedlineChernova, Tatiana A Yang, Zhen Karpova, Tatiana S Shanks, John R Shcherbik, Natalia Wilkinson, Keith D Chernoff, Yury O eng R01 GM114308/GM/NIGMS NIH HHS/ MCB 1817976/National Science Foundation/ R01GM114308/NH/NIH HHS/ R01GM093294/NH/NIH HHS/ Switzerland 2020/07/28 Int J Mol Sci. 2020 Jul 16; 21(14):5038. doi: 10.3390/ijms21145038" |
