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-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.
Sideri T, Yashiroda Y, Ellis DA, Rodríguez-López M, Yoshida M, Tuite MF, Bähler J