Li Xin, Zhang Yichun, Hu Ying, Tang Xiangrong, Gong Zishan, Lu Ren-Bin, Li Jia-da
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, Hunan, P. R. China.
Furong Laboratory, Department of Anaesthesiology, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, P. R. China.
Sci Rep. 2024 Dec 30;14(1):31605. doi: 10.1038/s41598-024-76981-y.
Dopamine (DA) plays important roles in various behaviors, including learning and motivation. Recently, THOC5 was identified as an important regulator in the development of dopaminergic neurons. However, how THOC5 is regulated has not been explored. In this study, we found an interaction between THOC5 and necdin, which is encoded by a gene located in the chromosome deletion region of Prader-Willi syndrome (PWS), by using a yeast two-hybrid assay. Necdin affects the mRNA export function of THOC5 by regulating its nucleocytoplasmic localization. As a result, the expression of a few DA neuronal development-related genes, such as Mef2c, Lef1 and Prkcg, is altered in necdin-deficient mice. We also found neurodegeneration of dopaminergic neurons and an increase of glial cells in necdin-deficient mice, which may underlie the dyspraxia behaviors in these mice. Our results thus identified necdin as a novel regulator for THOC5, which may underlie, at least partly, the abnormal DA neuron development in necdin-deficient mice.
多巴胺（DA）在包括学习和动机在内的各种行为中发挥着重要作用。最近，THOC5被确定为多巴胺能神经元发育中的一个重要调节因子。然而，THOC5是如何被调节的尚未得到探索。在本研究中，我们通过酵母双杂交试验发现THOC5与神经细胞黏附分子（necdin）之间存在相互作用，necdin由位于普拉德-威利综合征（PWS）染色体缺失区域的一个基因编码。Necdin通过调节THOC5的核质定位来影响其mRNA输出功能。结果，在缺乏necdin的小鼠中，一些与多巴胺能神经元发育相关的基因，如Mef2c、Lef1和Prkcg的表达发生了改变。我们还发现缺乏necdin的小鼠中多巴胺能神经元发生神经退行性变，神经胶质细胞增加，这可能是这些小鼠出现运动障碍行为的原因。因此，我们的结果确定necdin是THOC5的一种新型调节因子，这可能至少部分地解释了缺乏necdin的小鼠中多巴胺能神经元发育异常的原因。
