Coactivator-associated arginine methyltransferase 1 controls oligodendrocyte differentiation in the corpus callosum during early brain development.
Coactivator-associated arginine methyltransferase 1 controls oligodendrocyte differentiation in the corpus callosum during early brain development.
复制标题
共激活剂相关的精氨酸甲基转移酶 1 控制早期大脑发育过程中胼胝体中少突胶质细胞的分化。
DOI：
10.1002/dneu.22871
复制
发表时间：
2022
影响因子：
3
通讯作者：
Miyata S.
中科院分区：
文献类型：
--
作者：
Ishino Y;Shimizu S;Tohyama M;Miyata S.
蛋白精氨酸甲基化被认为是蛋白精氨酸甲基转移酶（Prmts）介导的精化蛋白功能的关键翻译后修饰之一。协同激活因子相关精氨酸甲基转移酶（Carm1，也称为Prmt4）通过其蛋白精氨酸甲基化活性参与各种细胞事件，如细胞存活、增殖和分化。Carm1调节神经细胞系的细胞增殖，据报道在哺乳动物大脑中表达。然而，它在中枢神经系统，特别是在胶质细胞中的详细功能，在很大程度上仍未被探索。在这项研究中，Carm1在发育中的大脑胼胝体中的少突胶质细胞（OL）谱系细胞中表现出相对较高的表达，随后在髓鞘形成活跃后显着下调。在分离的少突胶质前细胞（OPCs）中，抑制剂对Carm1活性的抑制减少了Ki67‐表达和BrdU‐结合的增殖细胞的数量。此外，通过可靠的髓磷脂相关标志物Plp的表达确定，Carm1失活减弱了OL的分化。它还损害了OL过程的延伸，伴随着与OL分化和髓鞘形成相关的基因表达的显著减少，如sox10、Cnp、Myrf和mbp。此外，OLs与胚胎背根神经节神经元共培养表明，Carm1活性对于神经元轴突周围髓磷脂过程和髓鞘的适当形成以及Ranvier结构分子节点Caspr的聚集是必需的。因此，我们认为Carm1是大脑发育过程中OPCs和OLs发育的重要分子。
Protein arginine methylation has been recognized as one of key posttranslational modifications for refined protein functions, mediated by protein arginine methyltransferases (Prmts). Coactivator‐associated arginine methyltransferase (Carm1, also known as Prmt4) participates in various cellular events, such as cell survival, proliferation, and differentiation through its protein arginine methylation activities. Carm1 regulates cell proliferation of a neuronal cell line and is reportedly expressed in the mammalian brain. However, its detailed function in the central nervous system, particularly in glial cells, remains largely unexplored. In this study, Carm1 exhibited relatively high expression in oligodendrocyte (OL) lineage cells present in the corpus callosum of the developing brain, followed by a remarkable downregulation after active myelination. The suppression of Carm1 activity by inhibitors in isolated oligodendrocyte precursor cells (OPCs) reduced the number of Ki67‐expressing and BrdU‐incorporated proliferating cells. Furthermore, Carm1 inactivation attenuated OL differentiation, as determined by the expression of Plp, a reliable myelin‐related marker. It also impaired the extension of OL processes, accompanied by a significant reduction in gene expression related to OL differentiation and myelination, such asSox10,Cnp,Myrf, andMbp. In addition, OLs co‐cultured with embryonic dorsal root ganglia neurons demonstrated that Carm1 activity is required for the appropriate formation of myelin processes and myelin sheaths around neuronal axons, and the induction of the clustering of Caspr, a node of Ranvier structural molecule. Thus, we propose that Carm1 is an essential molecule for the development of OPCs and OLs during brain development.