Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis

Reactive astrocytes play critical roles in the occurrence of various neurological diseases such as multiple sclerosis. Activation of astrocytes is often accompanied by a glycolysis-dominant metabolic switch. We found that PKM2 displayed nuclear translocation in astrocytes of EAE mice, an animal model of multiple sclerosis. And we identified the ubiquitination-mediated regulation of PKM2 nuclear import by ubiquitin ligase TRIM21. To detect the expression of TRM21 in EAE mice, We used single-cell sequencing to analyze the expression of TRM21 in EAE mice. In order to detect whether there were differences in the expression of TRIM21 in EAE mice at different stages, we compared normal mice with EAE mice in Peak and Chronic phases.

反应性星形胶质细胞在多发性硬化等多种神经系统疾病的发生过程中发挥关键作用。星形胶质细胞活化通常伴随以糖酵解为主的代谢转换。我们发现，在多发性硬化的动物模型——实验性自身免疫性脑脊髓炎（Experimental Autoimmune Encephalomyelitis, EAE）小鼠的星形胶质细胞中，丙酮酸激酶M2（PKM2）发生核转位。本研究明确了泛素连接酶TRIM21通过泛素化介导调控PKM2的核输入过程。为检测TRIM21在EAE小鼠中的表达情况，我们采用单细胞测序技术对EAE小鼠体内的TRIM21表达水平进行分析。为探究不同病程阶段EAE小鼠体内TRIM21的表达差异，我们将正常小鼠与发病高峰期、慢性期EAE小鼠的TRIM21表达水平进行了对比。