The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe.
The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants in Schizosaccharomyces pombe.
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DOI：
10.15698/mic2017.01.552
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Bähler J
中科院分区：
文献类型：
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作者：
Sideri T;Yashiroda Y;Ellis DA;Rodríguez-López M;Yoshida M;Tuite MF;Bähler J
朊病毒是一种基于蛋白质的传染性实体，与动物致命的脑部疾病有关，但也会改变芽殖酵母酿酒酵母中的一系列宿主细胞表型。关于朊病毒的进化和生物学还有许多问题。虽然在S. [HET-s]是唯一已知的其他真菌朊病毒。在这里，我们研究了裂殖酵母粟酒裂殖酵母中朊病毒样、基于蛋白质的表观遗传传递。我们证明了S.粟酒裂殖酵母细胞可以支持S.酿酒酵母Sup 35翻译因子[PSI+]，并且这些Sup 35聚集体的形成和繁殖被盐酸胍抑制，表明这些进化分歧的酵母中朊病毒繁殖机制的共性。一个蛋白质组范围的屏幕确定Ctr 4铜转运蛋白亚基作为一个假定的朊病毒与预测的朊病毒样结构域。Ctr 4基因的过表达导致大的Ctr 4蛋白聚集体，其是洗涤剂和蛋白酶K抗性的。携带这种[CTR+]聚集体的细胞表现出对氧化应激的敏感性增加，并且这种表型可以通过用[CTR+]细胞提取物转化而传递到无聚集体的[CTR-]细胞。此外，这种[CTR+]表型在与幼稚[ctr-]细胞交配后以非孟德尔方式遗传，但有趣的是，盐酸胍处理并没有消除[CTR+]表型。因此，Ctr 4表现出其他真菌朊病毒的多种特征，是裂殖酵母中朊病毒的第一个例子。这些研究结果表明，可传递的蛋白质为基础的性状的决定因素可能是真菌中更广泛的。
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.