Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
Sci Rep. 2020 Dec 4;10(1):21295. doi: 10.1038/s41598-020-78304-3.
The coiled-coil domain containing 50 (CCDC50) protein is a phosphotyrosine-dependent signalling protein stimulated by epidermal growth factor. It is highly expressed in neuronal cells in the central nervous system; however, the roles of CCDC50 in neuronal development are largely unknown. In this study, we showed that the depletion of CCDC50-V2 impeded the neuronal development process, including arbor formation, spine density development, and axonal outgrowth, in primary neurons. Mechanistic studies revealed that CCDC50-V2 positively regulated the nerve growth factor receptor, while it downregulated the epidermal growth factor receptor pathway. Importantly, JNK/c-Jun activation was found to be induced by the CCDC50-V2 overexpression, in which the interaction between CCDC50-V2 and JNK2 was also observed. Overall, the present study demonstrates a novel mechanism of CCDC50 function in neuronal development and provides new insight into the link between CCDC50 function and the aetiology of neurological disorders.
卷曲螺旋结构域蛋白 50(CCDC50)是一种由表皮生长因子刺激的磷酸酪氨酸依赖性信号蛋白。它在中枢神经系统的神经元细胞中高度表达;然而,CCDC50 在神经元发育中的作用在很大程度上尚不清楚。在这项研究中,我们表明 CCDC50-V2 的耗竭阻碍了原代神经元中的神经元发育过程,包括树突形成、棘密度发育和轴突生长。机制研究表明,CCDC50-V2 正向调节神经生长因子受体,同时下调表皮生长因子受体途径。重要的是,发现 JNK/c-Jun 的激活是由 CCDC50-V2 的过表达诱导的,在这种情况下,还观察到 CCDC50-V2 和 JNK2 之间的相互作用。总的来说,本研究证明了 CCDC50 在神经元发育中的新功能机制,并为 CCDC50 功能与神经疾病发病机制之间的联系提供了新的见解。