School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
J Mol Biol. 2011 May 6;408(3):432-48. doi: 10.1016/j.jmb.2011.02.034. Epub 2011 Mar 15.
Yeast prion [PSI(+)] is a self-perpetuating amyloid of the translational termination factor Sup35. Although [PSI(+)] propagation is modulated by heat shock proteins (Hsps), high temperature was previously reported to have little or no effect on [PSI(+)]. Our results show that short-term exposure of exponentially growing yeast culture to mild heat shock, followed by immediate resumption of growth, leads to [PSI(+)] destabilization, sometimes persisting for several cell divisions after heat shock. Prion loss occurring in the first division after heat shock is preferentially detected in a daughter cell, indicating the impairment of prion segregation that results in asymmetric prion distribution between a mother cell and a bud. Longer heat shock or prolonged incubation in the absence of nutrients after heat shock led to [PSI(+)] recovery. Both prion destabilization and recovery during heat shock depend on protein synthesis. Maximal prion destabilization coincides with maximal imbalance between Hsp104 and other Hsps such as Hsp70-Ssa. Deletions of individual SSA genes increase prion destabilization and/or counteract recovery. The dynamics of prion aggregation during destabilization and recovery are consistent with the notion that efficient prion fragmentation and segregation require a proper balance between Hsp104 and other (e.g., Hsp70-Ssa) chaperones. In contrast to heat shock, [PSI(+)] destabilization by osmotic stressors does not always depend on cell proliferation and/or protein synthesis, indicating that different stresses may impact the prion via different mechanisms. Our data demonstrate that heat stress causes asymmetric prion distribution in a cell division and confirm that the effects of Hsps on prions are physiologically relevant.
酵母朊病毒[PSI(+)]是一种自我维持的翻译终止因子 Sup35 的淀粉样蛋白。虽然[PSI(+)]的传播受到热休克蛋白（Hsps）的调节，但以前的研究表明高温对[PSI(+)]几乎没有影响。我们的研究结果表明，短时间暴露于温和热休克的指数生长酵母培养物，随后立即恢复生长，会导致[PSI(+)]失稳，有时在热休克后持续几个细胞分裂。在热休克后的第一次细胞分裂中发生的朊病毒丢失，优先在子细胞中检测到，表明朊病毒分离受损，导致母细胞和芽之间的朊病毒分布不对称。热休克后更长时间的热休克或在没有营养物质的情况下延长孵育时间会导致[PSI(+)]恢复。热休克过程中的朊病毒失稳和恢复都依赖于蛋白质合成。朊病毒最大失稳与 Hsp104 和其他 Hsp（如 Hsp70-Ssa）之间的最大失衡相一致。单个 SSA 基因的缺失增加了朊病毒的失稳和/或抵消了恢复。在失稳和恢复过程中朊病毒聚集的动力学与以下观点一致，即有效的朊病毒片段化和分离需要 Hsp104 和其他（如 Hsp70-Ssa）伴侣蛋白之间的适当平衡。与热休克不同，渗透压胁迫剂引起的[PSI(+)]失稳并不总是依赖于细胞增殖和/或蛋白质合成，这表明不同的应激可能通过不同的机制影响朊病毒。我们的数据表明，热应激导致细胞分裂中朊病毒分布不对称，并证实 Hsps 对朊病毒的影响在生理上是相关的。
