The orphan G protein-coupled receptor GPR149 is a negative regulator of myelination and remyelination
The orphan G protein-coupled receptor GPR149 is a negative regulator of myelination and remyelination
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孤儿 G 蛋白偶联受体 GPR149 是髓鞘形成和髓鞘再生的负调节因子
作者：
Suo, Na;He, Bingqing;Xie, Xin
髓鞘由中枢神经系统（CNS）的少突胶质细胞（OLs）和外周的雪旺细胞（Schwann cell）组成，在支持神经元功能方面起着关键作用。由少突胶质细胞前体细胞（OPCs）分化而来的OLs对发育过程中的髓鞘形成和CNS脱髓鞘疾病中的髓鞘修复至关重要。明确髓鞘损伤后髓鞘发育和髓鞘再生的机制具有重要的临床意义。在这里，我们表明，孤儿G蛋白偶联受体GPR 149，丰富的OPC，负调控OPC到OL分化，髓鞘形成，以及髓鞘再生。GPR 149的表达在OPCs向OLs分化过程中下调。GPR 149缺乏不影响OPC的数量，但促进OPC向OL分化，导致髓鞘的早期发育。在铜腙诱导的脱髓鞘模型中，GPR 149缺乏显著增强髓鞘再生。进一步的研究表明GPR 149可能通过MAPK/ERK途径调控OL分化和髓鞘形成。我们的研究表明，删除或阻断GPR 149可能是促进脱髓鞘疾病中髓鞘修复的一种有趣的方法。
Myelin sheath, formed by oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann cells in periphery, plays a critical role in supporting neuronal functions. OLs, differentiated from oligodendrocyte precursor cells (OPCs), are important for myelination during development and myelin repair in CNS demyelinating disease. To identify mechanisms of myelin development and remyelination after myelin damage is of great clinical interest. Here we show that the orphan G protein-coupled receptor GPR149, enriched in OPCs, negatively regulate OPC to OL differentiation, myelination, as well as remyelination. The expression of GPR149 is downregulated during OPCs differentiation into OLs. GPR149 deficiency does not affect the number of OPCs, but promotes OPC to OL differentiation which results in earlier development of myelin. In cuprizone-induced demyelination model, GPR149 deficiency significantly enhances myelin regeneration. Further study indicates that GPR149 may regulate OL differentiation and myelin formation via MAPK/ERK pathway. Our study suggests that deleting or blocking GPR149 might be an intriguing way to promote myelin repair in demyelinating diseases.