Solid-to-liquid phase transition in the dissolution of cytosolic misfolded-protein aggregates.
Solid-to-liquid phase transition in the dissolution of cytosolic misfolded-protein aggregates.
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DOI：
10.1016/j.isci.2023.108334
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发表时间：
2023-12-15
期刊：
影响因子：
5.8
通讯作者：
Li, Rong
中科院分区：
文献类型：
--
作者：
Tomaszewski, Alexis;Wang, Rebecca;Sandoval, Eduardo;Zhu, Jin;Liu, Jian;Li, Rong
蛋白质聚集体的积累是细胞衰老和退行性疾病的一个标志。这可能是由于蛋白质错误折叠和聚集增加，或者在应激下形成的聚集体溶解受损所致，而后者人们知之甚少。在这项研究中，我们采用定量活细胞成像技术来研究酵母中蛋白质解聚的动态过程。我们发现，热应激下形成的蛋白质聚集体是固态凝聚物，但在应激减弱后，这些蛋白质聚集体在溶解过程中首先转变为液态。这种固 - 液相变（SLPT）伴随着由于液态凝聚物融合而导致的聚集体数量减少。Hsp104是一种Clp/HSP100家族的分子伴侣，其分子伴侣活性对于固 - 液相变以及液态凝聚物随后的分散都是必需的。Sse1是一种酵母HSP110分子伴侣，它也促进固 - 液相变。这些结果阐明了一个在应激减弱时细胞对蛋白质解聚进行控制的意想不到的机制框架。
聚集体在应激减弱后经历固 - 液相变
溶解过程包括聚集，随后融合，尺寸和数量均减少
Hsp104对于固 - 液相变以及液态凝聚物随后的分散都是必需的
揭示了细胞对蛋白质解聚控制的一种意想不到的机制
生物科学；细胞生物学；生物化学
Accumulation of protein aggregates is a hallmark of cellular aging and degenerative disorders. This could result from either increased protein misfolding and aggregation or impaired dissolution of aggregates formed under stress, the latter of which is poorly understood. In this study, we employed quantitative live-cell imaging to investigate the dynamic process of protein disaggregation in yeast. We show that protein aggregates formed upon heat stress are solid condensates, but after stress attenuation these protein aggregates first transition into a liquid-like state during their dissolution. This solid-to-liquid phase transition (SLPT) accompanies the reduction in aggregate number due to the fusion of the liquid condensates. The chaperone activity of Hsp104, a Clp/HSP100 family chaperone, is required for both SLPT and subsequent dispersal of the liquid condensates. Sse1, a yeast HSP110 chaperone, also facilitates SLPT. These results illuminate an unexpected mechanistic framework of cellular control over protein disaggregation upon stress attenuation. Aggregates undergo a solid-to-liquid phase transition after stress attenuation Dissolution involves clustering followed by fusion reducing in both size and number Hsp104 is required for both SLPT and subsequent dispersal of the liquid condensates Reveal an unexpected mechanism of cellular control over protein disaggregation Biological sciences; Cell biology; Biochemistry
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影响因子：
5.3
作者：
Kaimal JM;Kandasamy G;Gasser F;Andréasson C
通讯作者：
Andréasson C
影响因子：
4.6
作者：
Gonçalves CC;Sharon I;Schmeing TM;Ramos CHI;Young JC
通讯作者：
Young JC
影响因子：
3
作者：
Boesl, Benjamin;Grimminger, Valerie;Walter, Stefan
通讯作者：
Walter, Stefan
DOI：
10.1073/pnas.152333299
发表时间：
2002-07-23
影响因子：
11.1
作者：
Jung, GM;Jones, G;Masison, DC
通讯作者：
Masison, DC
DOI：
10.1007/bf00330520
发表时间：
1986-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
HEINISCH, J
通讯作者：
HEINISCH, J