Toxicity and infectivity: insights from de novo prion formation.
Toxicity and infectivity: insights from de novo prion formation.
复制标题
毒性和感染力：从头形成的见解。
DOI：
10.1007/s00294-017-0736-1
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发表时间：
2018-03
期刊：
影响因子：
2.5
通讯作者：
Manogaran AL
中科院分区：
文献类型：
--
作者：
Wisniewski BT;Sharma J;Legan ER;Paulson E;Merrill SJ;Manogaran AL
朊病毒是一种感染性的错误折叠蛋白质，其组装成寡聚体和大的聚集体，并且与神经变性相关。据信，寡聚体有助于细胞毒性，尽管遗传和环境因素也已被证明具有额外的作用。对酵母朊病毒[PSI+]的研究为朊病毒如何形成以及为什么它们有毒提供了有价值的见解。我们最近的工作表明，SDS抗性寡聚体的出现和改造早期朊病毒形成过程中，裂解物含有这些新形成的寡聚体是传染性的。先前的工作表明，毒性与朊病毒的形成有关，并且这种毒性会因VPS5基因的缺失而加剧。在这里，我们表明新产生的寡聚体形成和vps5Δ裂解物的感染性与野生型菌株相似。然而，使用绿色荧光蛋白融合体，我们观察到在vps 5 Δ菌株中朊病毒形成期间荧光胞质聚集体的组装是不同的。vps 5 Δ菌株具有额外的小移动的病灶群体，而不是大的非移动的聚集体。我们推测，vps5Δ菌株细胞环境的变化可能会降低细胞有效招募和隔离新形成的朊病毒颗粒进入中心沉积部位的能力，从而导致毒性。
Prions are infectious misfolded proteins that assemble into oligomers and large aggregates, and are associated with neurodegeneration. It is believed that the oligomers contribute to cytotoxicity, although genetic and environmental factors have also been shown to have additional roles. The study of the yeast prion [PSI+] has provided valuable insights into how prions form and why they are toxic. Our recent work suggests that SDS-resistant oligomers arise and remodel early during the prion formation process, and lysates containing these newly formed oligomers are infectious. Previous work shows that toxicity is associated with prion formation and this toxicity is exacerbated by deletion of the VPS5 gene. Here, we show that newly made oligomer formation and infectivity of vps5Δ lysates are similar to wildtype strains. However using green fluorescent protein fusions, we observe that the assembly of fluorescent cytoplasmic aggregates during prion formation is different in vps5Δ strains. Instead of large immobile aggregates, vps5Δ strains have additional population of small mobile foci. We speculate that changes in the cellular milieu in vps5Δ strains may reduce the cell's ability to efficiently recruit and sequester newly formed prion particles into central deposition sites, resulting in toxicity.
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影响因子：
4.5
作者：
Arslan F;Hong JY;Kanneganti V;Park SK;Liebman SW
通讯作者：
Liebman SW
影响因子：
5.3
作者：
Du, Zhiqiang;Crow, Emily T.;Li, Liming
通讯作者：
Li, Liming
影响因子：
3.3
作者：
Horazdovsky, BF;Davies, BA;Emr, SD
通讯作者：
Emr, SD
DOI：
10.1080/10409238.2016.1226251
发表时间：
2016
影响因子：
6.5
作者：
Gerson JE;Mudher A;Kayed R
通讯作者：
Kayed R
影响因子：
3.3
作者：
Allen, KD;Wegrzyn, RD;Chernoff, YO
通讯作者：
Chernoff, YO