Quantitative proteomics reveals EVA1A-related proteins involved in neuronal differentiation
Quantitative proteomics reveals EVA1A-related proteins involved in neuronal differentiation
复制标题
定量蛋白质组学揭示 EVA1A 相关蛋白参与神经元分化
DOI：
10.1002/pmic.201600294
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发表时间：
2017
期刊：
影响因子：
3.4
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Zhong L;Zhou J;Chen X;Liu J;Liu Z;Chen Y;Bai Y
EVA 1A是一种自噬相关蛋白，在胚胎神经发生中发挥重要作用。在这项研究中，我们发现EVA 1A的缺失可以减少成年Eva 1a −/−小鼠大脑中的神经分化。为了确定这种表型背后的机制，我们使用Eva 1a −/−和野生型小鼠的大脑进行了无标记定量蛋白质组学和生物信息学分析。与野生型小鼠相比，我们在基因敲除小鼠的大脑中鉴定出11种上调的蛋白质和17种下调的蛋白质。生物信息学分析表明，生物过程，包括ATP的合成，氧化磷酸化，和TCA循环，参与了EVA 1A的调控网络。此外，基因集富集分析表明，神经退行性疾病，如阿尔茨海默病和亨廷顿病，与Eva 1 a基因敲除密切相关。蛋白质印迹实验表明，在Eva 1a基因敲除小鼠的大脑中，烟酰胺核苷酸转氢酶（一种参与TCA循环的重要线粒体酶）的表达发生了变化。我们的研究为Eva 1agene的分子功能和调控网络提供了有价值的信息，并为autography-related蛋白与神经分化之间的关系提供了新的视角。
EVA1A is an autophagy‐related protein, which plays an important role in embryonic neurogenesis. In this study, we found that loss of EVA1A could decrease neural differentiation in the brain of adultEva1a−/−mice. To determine the mechanism underlying this phenotype, we performed label‐free quantitative proteomics and bioinformatics analysis using the brains ofEva1a−/−and wild‐type mice. We identified 11 proteins that were up‐regulated and 17 that were down‐regulated in the brains of the knockout mice compared to the wild‐type counterparts. Bioinformatics analysis indicated that biological processes, including ATP synthesis, oxidative phosphorylation, and the TCA cycle, are involved in the EVA1A regulatory network. In addition, gene set enrichment analysis showed that neurodegenerative diseases, such as Alzheimer's disease and Huntington's disease, were strongly associated withEva1aknockout. Western blot experiments showed changes in the expression of nicotinamide nucleotide transhydrogenase, an important mitochondrial enzyme involved in the TCA cycle, in the brains ofEva1aknockout mice. Our study provides valuable information on the molecular functions and regulatory network of theEva1agene, as well as new perspectives on the relationship between autography‐related proteins and neural differentiation.