The role of pre-existing aggregates in Hsp104-dependent polyglutamine aggregate formation and epigenetic change of yeast prions
The role of pre-existing aggregates in Hsp104-dependent polyglutamine aggregate formation and epigenetic change of yeast prions
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DOI：
10.1111/j.1356-9597.2004.00759.x
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发表时间：
2004-08-01
期刊：
影响因子：
2.1
通讯作者：
Fujita, T
中科院分区：
文献类型：
--
作者：
Kimura, Y;Koitabashi, S;Fujita, T
淀粉样蛋白聚集体与多种疾病有关，也与酵母菌蛋白遗传有关。分子伴侣HSP104是酵母中聚谷氨酰胺聚合体形成所必需的，也是通过形成自繁殖聚合体来维持几种酵母蛋白表型所必需的。在这篇文章中，我们证明了独立于HSP104形成的聚谷氨酰胺聚集体是HSP104有效地产生更多聚集体所必需的。同样，在酵母[Psi+]系统中，依赖于Hsp104的[Psi+]Prion表观遗传改变需要正常[Psi(-)]状态下的Prion聚集体的存在。我们还表明，不同的Pron聚集体的共同定位表明，不同的酵母Pron的交叉播种增加了依赖于Hsp104的表观遗传变化的可能性。这些发现突显了预先存在的聚集体在依赖伴侣的酵母菌Pron中表观遗传特征的建立中的作用，并可能在几种神经退行性疾病的病理中发挥作用。
Amyloid-like protein aggregates have been implicated in various diseases and in the protein-based inheritance of yeast prions. The molecular chaperone Hsp104 has been shown to be necessary for the aggregate formation of polyglutamine in yeast, and for the maintenance of several yeast prion phenotypes through the formation of self-propagating aggregates. In this paper, we show that the polyglutamine aggregates that are formed independently of Hsp104, are required for Hsp104 to efficiently produce more aggregates. Similarly, in the yeast prion [PSI+] system, Hsp104-dependent epigenetic changes to the [PSI+] prion phenotype require the presence of prion aggregates in the normal [psi(-)] state. We also show that the co-localization of different prion aggregates suggests that cross-seeding by different yeast prions increases the probability of Hsp104-dependent epigenetic change. These findings highlight the role of pre-existing aggregates in chaperone-dependent establishment of the epigenetic trait in yeast prions, and possibly in the pathology of several neurodegenerative diseases.