title: The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants inSchizosaccharomyces pombe.
abstract: 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 inS. cerevisiae, [HET-s] ofPodospora anserinais the only other known fungal prion. Here we investigated prion-like, protein-based epigenetic transmission in the fission yeastSchizosaccharomyces pombe. We show thatS. pombecells can support the formation and maintenance of the prion form of theS. cerevisiaeSup35 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 thectr4gene 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.
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.
authors.forename: Theodora
authors.initials: T
authors.lastname: Sideri
authors.affiliation: Chemical Genetics Laboratory, RIKEN and Chemical Genomics Research Group, RIKEN CSRS, Saitama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yashiroda
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.
authors.forename: David A
authors.initials: DA
authors.lastname: Ellis
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-López
authors.affiliation: Chemical Genetics Laboratory, RIKEN and Chemical Genomics Research Group, RIKEN CSRS, Saitama, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Kent Fungal Group, University of Kent, School of Biosciences, Canterbury, Kent, U.K.
authors.forename: Mick F
authors.initials: MF
authors.lastname: Tuite
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Ageing, London, U.K.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
keywords: [PSI+]; meiosis; non-Mendelian segregation; oxidative stress; prion; protein aggregation; yeast