Department of Biological Sciences, Marquette University, Milwaukee, WI, USA.
Department of Mathematical and Statistical Sciences, Marquette University, Milwaukee, WI, USA.
Mol Microbiol. 2020 Sep;114(3):480-494. doi: 10.1111/mmi.14528. Epub 2020 Jun 8.
Chaperone networks are required for the shearing and generation of transmissible propagons from pre-existing prion aggregates. However, other cellular networks needed for maintaining yeast prions are largely uncharacterized. Here, we establish a novel role for actin networks in prion maintenance. The [PIN ] prion, also known as [RNQ ], exists as stable variants dependent upon the chaperone machinery for the transmission of propagons to daughter cells during cell division and cytoplasmic transfer. Loss of the Hsp104 molecular chaperone leads to the growth of prion particles until they are too large to be transmitted. Here, we isolated a unique [PIN ] variant, which is unstable in actin mutants. This prion loss is observed over many generations, and coincides with the detection of both high molecular weight species of Rnq1 and large visible aggregates that are asymmetrically retained during cell division. Our data suggest that the irregular actin networks found in these mutants may influence propagon number by slowly permitting aggregate growth over time, resulting in the generation of nontransmissible large aggregates. Thus, we show the potential contribution of cytoskeletal networks in the transmission of prion propagons, which parallels models that have been proposed for cell-to-cell transmission of small amyloids in neurodegenerative protein aggregation diseases.
伴侣蛋白网络对于从现有朊病毒聚集体中剪切和产生可传播的朊病毒是必需的。然而，用于维持酵母朊病毒的其他细胞网络在很大程度上尚未得到充分描述。在这里，我们确立了肌动蛋白网络在朊病毒维持中的新作用。[PIN]朊病毒，也称为[RNQ]，存在于稳定的变体中，这些变体依赖于伴侣蛋白机制，以便在细胞分裂和细胞质转移过程中将传播子传递给子细胞。Hsp104 分子伴侣的缺失会导致朊病毒颗粒的生长，直到它们太大而无法传递。在这里，我们分离到一种独特的[PIN]变体，它在肌动蛋白突变体中不稳定。这种朊病毒的丧失会在许多代中观察到，并且与 Rnq1 的高分子量物种以及在细胞分裂过程中不对称保留的大可见聚集体的检测同时发生。我们的数据表明，这些突变体中发现的不规则肌动蛋白网络可能会通过随着时间的推移缓慢允许聚集体生长来影响传播子的数量，从而产生不可传播的大聚集体。因此，我们展示了细胞骨架网络在朊病毒传播子传递中的潜在贡献，这与已经提出的用于神经退行性蛋白聚集疾病中小淀粉样蛋白的细胞间传递的模型相平行。
