Role of the Cell Asymmetry Apparatus and Ribosome-Associated Chaperones in the Destabilization of a Saccharomyces cerevisiae Prion by Heat Shock
Role of the Cell Asymmetry Apparatus and Ribosome-Associated Chaperones in the Destabilization of a Saccharomyces cerevisiae Prion by Heat Shock
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DOI：
10.1534/genetics.119.302237
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发表时间：
2019-07-01
期刊：
影响因子：
3.3
通讯作者：
Chernoff, Yury O.
中科院分区：
文献类型：
--
作者：
Howie, Rebecca L.;Jay-Garcia, Lina Manuela;Chernoff, Yury O.
自我延续的可传播蛋白质聚集体，称为朊病毒，与哺乳动物疾病有关，并控制酿酒酵母中可检测的表型特征。酵母应激诱导的伴侣蛋白，包括抵消细胞毒性蛋白聚集的 Hsp70-Ssa，也控制朊病毒的繁殖。热休克后的细胞分裂中，未被分子伴侣解聚的应激损伤蛋白质通过母体特异性不对称分离从子细胞中清除。短期轻度热应激会破坏[PSI+]（酵母翻译终止因子的一种朊病毒亚型）的稳定性。这种不稳定与伴侣的诱导有关。在这里，我们表明，已知的人工过量固化所需的区域也是热激介导的 [PSI+] 去稳定所需的区域。此外，编码对热损伤蛋白的不对称分离至关重要的脱乙酰酶的基因的缺失，也可以抵消热休克介导的[PSI+]不稳定，并且聚集体与由-GFP标记的热损伤蛋白聚集体共定位。这些结果支持不对称分离在朊病毒不稳定中的作用。最后，我们表明，热休克非诱导性核糖体相关伴侣 Hsp70-Ssb 的消耗减少了热休克介导的 [PSI+] 不稳定，而介导 Hsp70-Ssb 与核糖体结合的共伴侣复合物的破坏增加了朊病毒损失。我们的数据表明，热应激期间 Hsp70-Ssb 从核糖体迁移到细胞质。胞质 Hsp70-Ssb 已被证明可以拮抗 Hsp70-Ssa 在朊病毒增殖中的功能，这解释了 Hsp70-Ssb 对热休克引起的朊病毒不稳定的影响。这一结果揭示了应激非诱导伴侣的应激相关作用。自我永存的蛋白质聚集体（朊病毒）会导致哺乳动物疾病。酵母朊病毒在细胞分裂中具有遗传性。豪伊等人。证明负责细胞分裂不对称的细胞装置控制酵母朊病毒的不稳定......
Self-perpetuating transmissible protein aggregates, termed prions, are implicated in mammalian diseases and control phenotypically detectable traits in Saccharomyces cerevisiae. Yeast stress-inducible chaperone proteins, including and Hsp70-Ssa that counteract cytotoxic protein aggregation, also control prion propagation. Stress-damaged proteins that are not disaggregated by chaperones are cleared from daughter cells via mother-specific asymmetric segregation in cell divisions following heat shock. Short-term mild heat stress destabilizes [PSI+], a prion isoform of the yeast translation termination factor . This destabilization is linked to the induction of the chaperone. Here, we show that the region of known to be required for curing by artificially overproduced is also required for heat-shock-mediated [PSI+] destabilization. Moreover, deletion of the gene, coding for a deacetylase crucial for asymmetric segregation of heat-damaged proteins, also counteracts heat-shock-mediated destabilization of [PSI+], and aggregates are colocalized with aggregates of heat-damaged proteins marked by -GFP. These results support the role of asymmetric segregation in prion destabilization. Finally, we show that depletion of the heat-shock noninducible ribosome-associated chaperone Hsp70-Ssb decreases heat-shock-mediated destabilization of [PSI+], while disruption of a cochaperone complex mediating the binding of Hsp70-Ssb to the ribosome increases prion loss. Our data indicate that Hsp70-Ssb relocates from the ribosome to the cytosol during heat stress. Cytosolic Hsp70-Ssb has been shown to antagonize the function of Hsp70-Ssa in prion propagation, which explains the Hsp70-Ssb effect on prion destabilization by heat shock. This result uncovers the stress-related role of a stress noninducible chaperone.Self-perpetuating protein aggregates (prions) cause diseases in mammals. Yeast prions are heritable in cell divisions. Howie et al. demonstrate that the cellular apparatus responsible for the asymmetry of cell division controls destabilization of a yeast prion...