Investigating the Interactions of Yeast Prions: [SWI+], [PSI+], and [PIN+]
Investigating the Interactions of Yeast Prions: [SWI+], [PSI+], and [PIN+]
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DOI：
10.1534/genetics.114.163402
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发表时间：
2014-06-01
期刊：
影响因子：
3.3
通讯作者：
Li, Liming
中科院分区：
文献类型：
--
作者：
Du, Zhiqiang;Li, Liming
在出芽酵母（Saccharomyces cerevisiae）中发现了多个朊病毒元素，它们作为可遗传的蛋白质构象传播，通常与不同的表型有关。已有研究表明，当Sup35共同过量产生时，朊病毒蛋白Swi1的过量产生可以促进另一种酵母朊病毒[PSI+]的从头转化。然而，Pin(+) （[PSI+]诱导）活性的机制尚不清楚。此外，Swi1朊病毒（[SWI+]）如何与其他酵母朊病毒相互作用尚不清楚。在这里，我们证明了与Swi1过度生产相关的Pin（+）活性独立于Rnq1表达或[Pin +]转换。我们还发现[SWI+]增强了[PSI+]和[PIN+]的外观。然而，当[SWI+]共存时，[Pin +]显著地损害了[Pin +]的Pin（+）活性。我们进一步证明，单个酵母细胞可以同时携带三种朊病毒，[PSI+]， [PIN+]和[SWI+]。然而，在这种条件下，[SWI+]明显失稳。虽然聚集倾向是朊病毒发生的基础，但过量生产导致的Swi1和Rnq1聚集通常是不可遗传的。相反，在非过表达条件下形成的朊蛋白聚集体或由先前存在的朊蛋白诱导形成的朊蛋白聚集体更具有朊原性。对于重新形成的[PSI+]和[PIN+]，异源“促进剂”，如先前存在的[SWI+]聚集体，仅与新形成的环状/棒状Sup35或Rnq1聚集体共定位，而不与点状成熟朊病毒聚集体共定位。它们的共定位频率与它们的朊病毒诱导性相协调，表明朊病毒与朊病毒的相互作用主要发生在起始阶段的早期。我们的研究结果为朊病毒发生的交叉播种模型提供了支持证据，并突出了酵母中朊病毒之间复杂的相互作用网络。
Multiple prion elements, which are transmitted as heritable protein conformations and often linked to distinct phenotypes, have been identified in the budding yeast, Saccharomyces cerevisiae. It has been shown that overproduction of a prion protein Swi1 can promote the de novo conversion of another yeast prion [PSI+] when Sup35 is co-overproduced. However, the mechanism underlying this Pin(+) ([PSI+] inducible) activity is not clear. Moreover, how the Swi1 prion ([SWI+]) interacts with other yeast prions is unknown. Here, we demonstrate that the Pin(+) activity associated with Swi1 overproduction is independent of Rnq1 expression or [PIN+] conversion. We also show that [SWI+] enhances the appearance of [PSI+] and [PIN+]. However, [SWI+] significantly compromises the Pin(+) activity of [PIN+] when they coexist. We further demonstrate that a single yeast cell can harbor three prions, [PSI+], [PIN+], and [SWI+], simultaneously. However, under this condition, [SWI+] is significantly destabilized. While the propensity to aggregate underlies prionogenesis, Swi1 and Rnq1 aggregates resulting from overproduction are usually nonheritable. Conversely, prion protein aggregates formed in nonoverexpressing conditions or induced by preexisting prion(s) are more prionogenic. For [PSI+] and [PIN+] de novo formation, heterologous "facilitators," such as preexisting [SWI+] aggregates, colocalize only with the newly formed ring-/rod-shaped Sup35 or Rnq1 aggregates, but not with the dot-shaped mature prion aggregates. Their colocalization frequency is coordinated with their prion inducibility, indicating that prion-prion interactions mainly occur at the early initiation stage. Our results provide supportive evidence for the cross-seeding model of prionogenesis and highlight a complex interaction network among prions in yeast.