Reference - PMID:28191457 - The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe .
Reference summary
- PubMed ID
- PMID:28191457
- Title
- The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe .
- Authors
- Sideri T, Yashiroda Y, Ellis DA, Rodríguez-López M, Yoshida M, Tuite MF, Bähler J
- Citation
- Microb Cell 2017 Jan;4(1):16-28
- Publication year
- 2017
- 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 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.
