Analysis of novel hyperosmotic shock response suggests 'beads in liquid' cytosol structure
Analysis of novel hyperosmotic shock response suggests 'beads in liquid' cytosol structure
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DOI：
10.1242/bio.044529
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发表时间：
2019-07-01
期刊：
影响因子：
2.4
通讯作者：
Agaphonov, Michael O.
中科院分区：
文献类型：
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作者：
Alexandrov, Alexander, I;Grosfeld, Erika, V;Agaphonov, Michael O.
蛋白质可以在应激反应中聚集，包括高渗休克。聚集体的形成和分解是一个相对缓慢的过程。我们描述了一种新的即时响应的细胞高渗透，在此期间，伴侣蛋白和其他蛋白质形成许多焦点与经典的聚集体的特性。这些病灶在休克发作/解除后数秒出现/消失，与细胞体积变化密切相关。全基因组和靶向检测揭示了病灶中的伴侣蛋白、代谢酶、P体组分和淀粉样蛋白。这些蛋白质中的大多数可以形成大的组装体，并且对于一些，组装状态是参与焦点的先决条件。全基因组筛选未能确定基因的缺乏阻止灶参与热休克蛋白70。超分辨率显微镜显示的病灶之间的相互连接表明病灶被其他实体压缩。基于我们的研究结果，我们提出了一个新的模型的细胞质结构作为一个集合的众多的凝胶状区域悬浮在一个液体网络。该网络响应于高渗透而体积减小，并在凝胶状区域之间形成小口袋。
Proteins can aggregate in response to stresses, including hyperosmotic shock. Formation and disassembly of aggregates is a relatively slow process. We describe a novel instant response of the cell to hyperosmosis, during which chaperones and other proteins form numerous foci with properties uncharacteristic of classical aggregates. These foci appeared/disappeared seconds after shock onset/removal, in close correlation with cell volume changes. Genome-wide and targeted testing revealed chaperones, metabolic enzymes, P-body components and amyloidogenic proteins in the foci. Most of these proteins can form large assemblies and for some, the assembled state was pre-requisite for participation in foci. A genome-wide screen failed to identify genes whose absence prevented foci participation by Hsp70. Shapes of and interconnections between foci, revealed by super-resolution microscopy, indicated that the foci were compressed between other entities. Based on our findings, we suggest a new model of cytosol architecture as a collection of numerous gel-like regions suspended in a liquid network. This network is reduced in volume in response to hyperosmosis and forms small pockets between the gel-like regions.