Prion-dependent proteome remodeling in response to environmental stress is modulated by prion variant and genetic background.
Prion-dependent proteome remodeling in response to environmental stress is modulated by prion variant and genetic background.
复制标题
响应环境压力的朊病毒依赖性蛋白质组重塑受到朊病毒变异和遗传背景的调节。
DOI：
10.1080/19336896.2019.1583041
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发表时间：
2019
期刊：
影响因子：
2.3
通讯作者：
Cameron,DaleM
中科院分区：
文献类型：
--
作者：
Allwein,Ben;Kelly,Christina;Kammoonah,Shaima;Mayor,Thibault;Cameron,DaleM
许多真菌蛋白质能够采用多种可供选择的、自我永续的普恩构象。这些蛋白变异与形成蛋白的功能变化有关，从而产生了有害或有益的新的、可遗传的特征。在这里，我们试图确定先前报道的含有[PSI+]Prion的酵母对ZnCl2敏感的特性在多大程度上受到遗传背景和Prion变体的调节，以及这种特性是否伴随着依赖于Prion的蛋白质组变化，从而阐明其生理基础。我们还检查了普恩变异和遗传背景对其他普恩依赖表型的影响程度。我们发现，与[psi−]细胞相比，接触氯化锌不仅减少了集落生长，还限制了[psi+]细胞的时间寿命。在S288C和W303的遗传背景中，观察到多个Prion变异体的生存能力下降。蛋白质组定量分析显示，与[psi−]细胞相比，[psi+]细胞应激反应蛋白表达增加，参与能量代谢的蛋白表达降低。这些结果表明，细胞压力和生长减慢是我们观察到的表型的基础。更广泛地说，我们发现Pron变异和遗传背景调节蛋白丰度依赖于Prion的变化，并可以深刻地影响在不同环境中的生存能力。因此，获得Pron变异体的星座与遗传变异的积累相结合，有可能显著增加酵母种群的表型多样性，从而增强其在不断变化的环境条件下的适应潜力。
A number of fungal proteins are capable of adopting multiple alternative, self-perpetuating prion conformations. These prion variants are associated with functional alterations of the prion-forming protein and thus the generation of new, heritable traits that can be detrimental or beneficial. Here we sought to determine the extent to which the previously-reported ZnCl2-sensitivity trait of yeast harboring the [PSI+] prion is modulated by genetic background and prion variant, and whether this trait is accompanied by prion-dependent proteomic changes that could illuminate its physiological basis. We also examined the degree to which prion variant and genetic background influence other prion-dependent phenotypes. We found that ZnCl2exposure not only reduces colony growth but also limits chronological lifespan of [PSI+] relative to [psi−] cells. This reduction in viability was observed for multiple prion variants in both the S288C and W303 genetic backgrounds. Quantitative proteomic analysis revealed that under exposure to ZnCl2the expression of stress response proteins was elevated and the expression of proteins involved in energy metabolism was reduced in [PSI+] relative to [psi−] cells. These results suggest that cellular stress and slowed growth underlie the phenotypes we observed. More broadly, we found that prion variant and genetic background modulate prion-dependent changes in protein abundance and can profoundly impact viability in diverse environments. Thus, access to a constellation of prion variants combined with the accumulation of genetic variation together have the potential to substantially increase phenotypic diversity within a yeast population, and therefore to enhance its adaptation potential in changing environmental conditions.