The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe
Prions are protein-based infectious entities associated with fatal brain diseases in animals, but also modify a range of host-cell phenotypes in the budding yeast, Saccharomyces cerevisiae. Many questions remain about the evolution and biology of prions. Although several functionally distinct prion-...
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Shared Science Publishers OG
2017-01-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/the-copper-transport-associated-protein-ctr4-can-form-prion-like-epigenetic-determinants-in-schizosaccharomyces-pombe/ |
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| author | Theodora Sideri Yoko Yashiroda David A. Ellis María Rodríguez-López Minoru Yoshida Mick F. Tuite Jürg Bähler |
| author_facet | Theodora Sideri Yoko Yashiroda David A. Ellis María Rodríguez-López Minoru Yoshida Mick F. Tuite Jürg Bähler |
| author_sort | Theodora Sideri |
| collection | DOAJ |
| description | Prions are protein-based infectious entities associated with fatal brain diseases in animals, but also modify a range of host-cell phenotypes in the budding yeast, Saccharomyces cerevisiae. Many questions remain about the evolution and biology of prions. Although several functionally distinct prion-forming proteins exist in S. cerevisiae, [HET-s] of Podospora anserina is the only other known fungal prion. Here we investigated prion-like, protein-based epigenetic transmission in the fission yeast Schizosaccharomyces pombe. We show that S. pombe cells can support the formation and maintenance of the prion form of the S. cerevisiae Sup35 translation factor [PSI+], and that the formation and propagation of these Sup35 aggregates is inhibited by guanidine hydrochloride, indicating commonalities in prion propagation machineries in these evolutionary diverged yeasts. A proteome-wide screen identified the Ctr4 copper transporter subunit as a putative prion with a predicted prion-like domain. Overexpression of the ctr4 gene resulted in large Ctr4 protein aggregates that were both detergent and proteinase-K resistant. Cells carrying such [CTR+] aggregates showed increased sensitivity to oxidative stress, and this phenotype could be transmitted to aggregate-free [ctr–] cells by transformation with [CTR+] cell extracts. Moreover, this [CTR+] phenotype was inherited in a non-Mendelian manner following mating with naïve [ctr–] cells, but intriguingly the [CTR+] phenotype was not eliminated by guanidine-hydrochloride treatment. Thus, Ctr4 exhibits multiple features diagnostic of other fungal prions and is the first example of a prion in fission yeast. These findings suggest that transmissible protein-based determinants of traits may be more widespread among fungi. |
| format | Article |
| id | doaj-art-e3e392c7436f48edabff38d25858c3d9 |
| institution | DOAJ |
| issn | 2311-2638 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Shared Science Publishers OG |
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| series | Microbial Cell |
| spelling | doaj-art-e3e392c7436f48edabff38d25858c3d92025-08-20T02:57:39ZengShared Science Publishers OGMicrobial Cell2311-26382017-01-0141162810.15698/mic2017.01.552The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombeTheodora Sideri0Yoko Yashiroda1David A. Ellis2María Rodríguez-López3Minoru Yoshida4Mick F. Tuite5Jürg Bähler6University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.Chemical Genetics Laboratory, RIKEN and Chemical Genomics Research Group, RIKEN CSRS, Saitama, Japan.University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.Chemical Genetics Laboratory, RIKEN and Chemical Genomics Research Group, RIKEN CSRS, Saitama, Japan.Kent Fungal Group, University of Kent, School of Biosciences, Canterbury, Kent, U.K.University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.Prions are protein-based infectious entities associated with fatal brain diseases in animals, but also modify a range of host-cell phenotypes in the budding yeast, Saccharomyces cerevisiae. Many questions remain about the evolution and biology of prions. Although several functionally distinct prion-forming proteins exist in S. cerevisiae, [HET-s] of Podospora anserina is the only other known fungal prion. Here we investigated prion-like, protein-based epigenetic transmission in the fission yeast Schizosaccharomyces pombe. We show that S. pombe cells can support the formation and maintenance of the prion form of the S. cerevisiae Sup35 translation factor [PSI+], and that the formation and propagation of these Sup35 aggregates is inhibited by guanidine hydrochloride, indicating commonalities in prion propagation machineries in these evolutionary diverged yeasts. A proteome-wide screen identified the Ctr4 copper transporter subunit as a putative prion with a predicted prion-like domain. Overexpression of the ctr4 gene resulted in large Ctr4 protein aggregates that were both detergent and proteinase-K resistant. Cells carrying such [CTR+] aggregates showed increased sensitivity to oxidative stress, and this phenotype could be transmitted to aggregate-free [ctr–] cells by transformation with [CTR+] cell extracts. Moreover, this [CTR+] phenotype was inherited in a non-Mendelian manner following mating with naïve [ctr–] cells, but intriguingly the [CTR+] phenotype was not eliminated by guanidine-hydrochloride treatment. Thus, Ctr4 exhibits multiple features diagnostic of other fungal prions and is the first example of a prion in fission yeast. These findings suggest that transmissible protein-based determinants of traits may be more widespread among fungi.http://microbialcell.com/researcharticles/the-copper-transport-associated-protein-ctr4-can-form-prion-like-epigenetic-determinants-in-schizosaccharomyces-pombe/yeastprionprotein aggregation [PSI+]meiosisnon-Mendelian segregationoxidative stress |
| spellingShingle | Theodora Sideri Yoko Yashiroda David A. Ellis María Rodríguez-López Minoru Yoshida Mick F. Tuite Jürg Bähler The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe Microbial Cell yeast prion protein aggregation [PSI+] meiosis non-Mendelian segregation oxidative stress |
| title | The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe |
| title_full | The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe |
| title_fullStr | The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe |
| title_full_unstemmed | The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe |
| title_short | The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe |
| title_sort | copper transport associated protein ctr4 can form prion like epigenetic determinants in schizosaccharomyces pombe |
| topic | yeast prion protein aggregation [PSI+] meiosis non-Mendelian segregation oxidative stress |
| url | http://microbialcell.com/researcharticles/the-copper-transport-associated-protein-ctr4-can-form-prion-like-epigenetic-determinants-in-schizosaccharomyces-pombe/ |
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