Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Max Planck Institute of Experimental Medicine, Proteomics Group, Göttingen, Germany.
Aging Cell. 2018 Aug;17(4):e12760. doi: 10.1111/acel.12760. Epub 2018 Apr 6.
A proper equilibrium of post-translational protein modifications is essential for normal cell physiology, and alteration in these processes is key in neurodegenerative disorders such as Alzheimer's disease. Recently, for instance, alteration in protein SUMOylation has been linked to amyloid pathology. In this work, we aimed to elucidate the role of protein SUMOylation during aging and increased amyloid burden in vivo using a His -HA-SUMO1 knock-in mouse in the 5XFAD model of Alzheimer's disease. Interestingly, we did not observe any alteration in the levels of SUMO1-conjugation related to Alzheimer's disease. SUMO1 conjugates remained localized to neuronal nuclei upon increased amyloid burden and during aging and were not detected in amyloid plaques. Surprisingly however, we observed age-related alterations in global levels of SUMO1 conjugation and at the level of individual substrates using quantitative proteomic analysis. The identified SUMO1 candidate substrates are dominantly nuclear proteins, mainly involved in RNA processing. Our findings open novel directions of research for studying a functional link between SUMOylation and its role in guarding nuclear functions during aging.
蛋白质翻译后修饰的适当平衡对于正常的细胞生理学至关重要，这些过程的改变是阿尔茨海默病等神经退行性疾病的关键。例如，最近蛋白质 SUMO 化的改变与淀粉样蛋白病理学有关。在这项工作中，我们使用阿尔茨海默病 5XFAD 模型中的 His-HA-SUMO1 敲入小鼠，旨在阐明蛋白质 SUMO 化在衰老和体内淀粉样蛋白负担增加过程中的作用。有趣的是，我们没有观察到与阿尔茨海默病相关的 SUMO1 缀合水平的任何改变。SUMO1 缀合物在淀粉样蛋白负荷增加和衰老时仍然定位于神经元核内，并且不在淀粉样斑块中检测到。然而，令人惊讶的是，我们使用定量蛋白质组学分析观察到与年龄相关的 SUMO1 缀合的整体水平和个别底物的改变。鉴定的 SUMO1 候选底物主要是核蛋白，主要参与 RNA 加工。我们的发现为研究 SUMO 化及其在衰老过程中保护核功能方面的功能联系开辟了新的研究方向。
