Hsp104-dependent remodeling of prion complexes mediates protein-only inheritance
Hsp104-dependent remodeling of prion complexes mediates protein-only inheritance
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DOI：
10.1371/journal.pbio.0050024
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发表时间：
2007-02-01
期刊：
影响因子：
9.8
通讯作者：
Serio, Tricia R.
中科院分区：
文献类型：
--
作者：
Satpute-Krishnan, Prasanna;Langseth, Sara X.;Serio, Tricia R.
表型性状的遗传取决于两个关键事件：该性状决定因子的复制和这些拷贝在母细胞和子细胞之间的分配。尽管这些过程对于基于核酸的基因是很好理解的，但是对于仅基于蛋白质或基于朊病毒的遗传元件指导表型遗传的机制知之甚少。在这里，我们报告的酿酒酵母朊病毒[PSI+]，Sup 35蛋白的自我复制构象的遗传至关重要的过程。通过严格控制Sup 35-GFP融合体的表达，我们直接观察了体内现有Sup 35（[PSI+]）复合物的重塑。当分子伴侣Hsp 104（所有酵母朊病毒繁殖所必需的因子）功能受损时，Sup 35（[PSI+]）的这种动态变化消失。HSP 104对Sup 35（[PSI+]）重塑的损失降低了这些复合物在胞质溶胶中的流动性，产生了限制其传递到子细胞的分离偏倚，并因此降低了新产生的Sup 35转化为朊病毒形式的效率。我们的观察解决了几个看似相互矛盾的报告的机制Hsp 104的行动，并指出一个单一的Hsp 104依赖的事件朊病毒传播。
Inheritance of phenotypic traits depends on two key events: replication of the determinant of that trait and partitioning of these copies between mother and daughter cells. Although these processes are well understood for nucleic acid-based genes, the mechanisms by which protein-only or prion-based genetic elements direct phenotypic inheritance are poorly understood. Here, we report a process crucial for inheritance of the Saccharomyces cerevisiae prion [PSI+], a self-replicating conformer of the Sup35 protein. By tightly controlling expression of a Sup35-GFP fusion, we directly observe remodeling of existing Sup35([PSI+]) complexes in vivo. This dynamic change in Sup35([PSI+]) is lost when the molecular chaperone Hsp104, a factor essential for propagation of all yeast prions, is functionally impaired. The loss of Sup35([PSI+]) remodeling by Hsp104 decreases the mobility of these complexes in the cytosol, creates a segregation bias that limits their transmission to daughter cells, and consequently diminishes the efficiency of conversion of newly made Sup35 to the prion form. Our observations resolve several seemingly conflicting reports on the mechanism of Hsp104 action and point to a single Hsp104-dependent event in prion propagation.