Cellular growth defects triggered by an overload of protein localization processes.
Cellular growth defects triggered by an overload of protein localization processes.
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DOI：
10.1038/srep31774
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发表时间：
2016-08-19
影响因子：
4.6
通讯作者：
Moriya H
中科院分区：
文献类型：
--
作者：
Kintaka R;Makanae K;Moriya H
定位于细胞内区室的蛋白质的高水平表达预期会导致细胞缺陷，因为它使定位过程过载。然而，超载的本地化过程从来没有被系统地研究。在这里，我们表明，表达水平的绿色荧光蛋白（GFP）与本地化信号被限制到相同的程度作为一个有毒的错误折叠的绿色荧光蛋白在芽殖酵母细胞，和它们的高水平表达引起的细胞缺陷与本地化过程。我们进一步表明，限制exportin Crm1决定了GFP的表达限制与核输出信号。虽然错误折叠的绿色荧光蛋白与囊泡介导的运输信号触发内质网应激，它不是其表达限制的主要决定因素。具有线粒体靶向信号的GFP前体引起细胞缺陷。最后，我们估计了局部化过程的剩余容量。因此，定位蛋白的高水平表达通过使定位过程的能力过载而导致细胞缺陷。
High-level expression of a protein localized to an intracellular compartment is expected to cause cellular defects because it overloads localization processes. However, overloads of localization processes have never been studied systematically. Here, we show that the expression levels of green fluorescent proteins (GFPs) with localization signals were limited to the same degree as a toxic misfolded GFP in budding yeast cells, and that their high-level expression caused cellular defects associated with localization processes. We further show that limitation of the exportin Crm1 determined the expression limit of GFP with a nuclear export signal. Although misfolding of GFP with a vesicle-mediated transport signal triggered endoplasmic reticulum stress, it was not the primary determinant of its expression limit. The precursor of GFP with a mitochondrial targeting signal caused a cellular defect. Finally, we estimated the residual capacities of localization processes. High-level expression of a localized protein thus causes cellular defects by overloading the capacities of localization processes.