Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association
Yeast prions and mnemons are respectively transmissible and non-transmissible self-perpetuating protein assemblies, frequently based on cross-β ordered detergent-resistant aggregates (amyloids). Prions cause devastating diseases in mammals and control heritable traits in yeast. It was shown that the...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/5038 |
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| author | Tatiana A. Chernova Zhen Yang Tatiana S. Karpova John R. Shanks Natalia Shcherbik Keith D. Wilkinson Yury O. Chernoff |
| author_facet | Tatiana A. Chernova Zhen Yang Tatiana S. Karpova John R. Shanks Natalia Shcherbik Keith D. Wilkinson Yury O. Chernoff |
| author_sort | Tatiana A. Chernova |
| collection | DOAJ |
| description | Yeast prions and mnemons are respectively transmissible and non-transmissible self-perpetuating protein assemblies, frequently based on cross-β 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 [<i>PSI</i><sup>+</sup>] of yeast release factor Sup35 is facilitated by aggregates of other proteins. Here we explore the mechanism of the promotion of [<i>PSI</i><sup>+</sup>] 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 [<i>PSI</i><sup>+</sup>] 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. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:25:18Z |
| publishDate | 2020-07-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0bf5e9805ecf4e128bdb0a7957a5cc912023-11-20T07:01:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114503810.3390/ijms21145038Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane AssociationTatiana A. Chernova0Zhen Yang1Tatiana S. Karpova2John R. Shanks3Natalia Shcherbik4Keith D. Wilkinson5Yury O. Chernoff6Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USACenter for Cancer Research Core Fluorescence Imaging Facility, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Cell Biology, Rowan University, School of Osteopathic Medicine, Stratford, NJ 08084, USADepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USASchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332-2000, USAYeast prions and mnemons are respectively transmissible and non-transmissible self-perpetuating protein assemblies, frequently based on cross-β 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 [<i>PSI</i><sup>+</sup>] of yeast release factor Sup35 is facilitated by aggregates of other proteins. Here we explore the mechanism of the promotion of [<i>PSI</i><sup>+</sup>] 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 [<i>PSI</i><sup>+</sup>] 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.https://www.mdpi.com/1422-0067/21/14/5038prionamyloidmnemonmatingG-proteinSup35 |
| spellingShingle | Tatiana A. Chernova Zhen Yang Tatiana S. Karpova John R. Shanks Natalia Shcherbik Keith D. Wilkinson Yury O. Chernoff Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association International Journal of Molecular Sciences prion amyloid mnemon mating G-protein Sup35 |
| title | Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association |
| title_full | Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association |
| title_fullStr | Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association |
| title_full_unstemmed | Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association |
| title_short | Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association |
| title_sort | aggregation and prion inducing properties of the g protein gamma subunit ste18 are regulated by membrane association |
| topic | prion amyloid mnemon mating G-protein Sup35 |
| url | https://www.mdpi.com/1422-0067/21/14/5038 |
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