The Number and Transmission of [PSI+] Prion Seeds (Propagons) in the Yeast Saccharomyces cerevisiae
The Number and Transmission of [PSI+] Prion Seeds (Propagons) in the Yeast Saccharomyces cerevisiae
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DOI：
10.1371/journal.pone.0004670
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发表时间：
2009-03-05
期刊：
影响因子：
3.7
通讯作者：
Tuite, Mick F.
中科院分区：
文献类型：
--
作者：
Byrne, Lee J.;Cole, Diana J.;Tuite, Mick F.
背景：酵母（Saccharomyces cerevisiae）的朊病毒是有效繁殖的，在细胞分裂过程中，朊病毒种子（繁殖体）不断产生和传递给子细胞，确保了高度的有丝分裂稳定性。盐酸胍（GdnHCl）对分子伴侣Hsp104p的可逆抑制导致酵母朊病毒的细胞分裂依赖性消除，这是由于繁殖体产生的阻断和随后的繁殖体被细胞分裂稀释。主要发现：分析gdnhcl诱导的酵母[PSI+]朊病毒消除的动力学，使我们能够开发新的统计模型，帮助我们了解朊病毒在酵母细胞中的传播。在这里，我们描述了一种新的随机模型的应用，该模型使我们能够更准确地估计[PSI+]细胞中传播体的平均数量。为了达到这种准确性，我们还通过实验确定了关键的细胞繁殖参数，并表明[PSI+]朊病毒的存在对这些关键过程没有影响。此外，我们通过实验确定了传递给子细胞的繁殖体的比例，并表明这反映了细胞分裂时母细胞和子细胞的相对细胞体积。结论：虽然繁殖体的产生是一个atp驱动的过程，但繁殖体向子细胞的分裂是通过细胞质分布的被动转移发生的。此外，我们对n(0)的新估计，即每个细胞（500-1000）的繁殖体数量，比我们以前的估计高出约5倍，这对我们理解[PSI+]的遗传和无朊病毒细胞的自发形成具有重要意义。
Background: Yeast (Saccharomyces cerevisiae) prions are efficiently propagated and the on-going generation and transmission of prion seeds (propagons) to daughter cells during cell division ensures a high degree of mitotic stability. The reversible inhibition of the molecular chaperone Hsp104p by guanidine hydrochloride (GdnHCl) results in cell division-dependent elimination of yeast prions due to a block in propagon generation and the subsequent dilution out of propagons by cell division.Principal Findings: Analysing the kinetics of the GdnHCl-induced elimination of the yeast [PSI+] prion has allowed us to develop novel statistical models that aid our understanding of prion propagation in yeast cells. Here we describe the application of a new stochastic model that allows us to estimate more accurately the mean number of propagons in a [PSI+] cell. To achieve this accuracy we also experimentally determine key cell reproduction parameters and show that the presence of the [PSI+] prion has no impact on these key processes. Additionally, we experimentally determine the proportion of propagons transmitted to a daughter cell and show this reflects the relative cell volume of mother and daughter cells at cell division.Conclusions: While propagon generation is an ATP-driven process, the partition of propagons to daughter cells occurs by passive transfer via the distribution of cytoplasm. Furthermore, our new estimates of n(0), the number of propagons per cell (500-1000), are some five times higher than our previous estimates and this has important implications for our understanding of the inheritance of the [PSI+] and the spontaneous formation of prion-free cells.