A heritable switch in carbon source utilization driven by an unusual yeast prion
A heritable switch in carbon source utilization driven by an unusual yeast prion
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DOI：
10.1101/gad.1839109
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发表时间：
2009-10-01
影响因子：
10.5
通讯作者：
Lindquist, Susan
中科院分区：
文献类型：
--
作者：
Brown, Jessica C. S.;Lindquist, Susan
几种特性良好的真菌蛋白作为朊病毒，具有多种构象的蛋白质，每种具有不同的活性，其中至少有一种是自我繁殖的。通过这种自我繁殖的功能改变，酵母朊病毒作为表型遗传的蛋白质基础元件。我们报道了一种朊病毒，它可以使细胞抵抗葡萄糖相关抑制的替代碳源，[GAR(+)]（大写字母表示抵抗葡萄糖相关抑制，括号表示其非孟德尔特征）。[GAR(+)]以高速率自发出现，并通过非孟德尔的细胞质遗传传播。一些证据表明，朊病毒状态涉及一小部分细胞补体Pma1（主要的质膜质子泵）和Std1（一种丰度低得多的参与葡萄糖信号传导的蛋白质）之间的复合物。来自密切相关的酵母菌种的Pma1蛋白也与[GAR(+)]的出现有关。通过建立Pma1、Std1和[GAR(+)]蛋白在酿酒酵母中为朊病毒的繁殖和诱导创造传播屏障，我们确认了Pma1、Std1和[GAR(+)]之间的关系。酵母细胞使用基于朊病毒的机制在不同的碳源利用策略之间进行遗传切换，并使用质膜质子泵来完成这一过程，这一事实扩展了自繁殖的基于蛋白质的遗传元件运作的生物学框架。
Several well-characterized fungal proteins act as prions, proteins capable of multiple conformations, each with different activities, at least one of which is self-propagating. Through such self-propagating changes in function, yeast prions act as protein-based elements of phenotypic inheritance. We report a prion that makes cells resistant to the glucose-associated repression of alternative carbon sources, [GAR(+)] (for "resistant to glucose-associated repression," with capital letters indicating dominance and brackets indicating its non-Mendelian character). [GAR(+)] appears spontaneously at a high rate and is transmissible by non-Mendelian, cytoplasmic inheritance. Several lines of evidence suggest that the prion state involves a complex between a small fraction of the cellular complement of Pma1, the major plasma membrane proton pump, and Std1, a much lower-abundance protein that participates in glucose signaling. The Pma1 proteins from closely related Saccharomyces species are also associated with the appearance of [GAR(+)]. This allowed us to confirm the relationship between Pma1, Std1, and [GAR(+)] by establishing that these proteins can create a transmission barrier for prion propagation and induction in Saccharomyces cerevisiae. The fact that yeast cells employ a prion-based mechanism for heritably switching between distinct carbon source utilization strategies, and employ the plasma membrane proton pump to do so, expands the biological framework in which self-propagating protein-based elements of inheritance operate.