Slit2 Regulates the Dispersal of Oligodendrocyte Precursor Cells via Fyn/RhoA Signaling
Slit2 Regulates the Dispersal of Oligodendrocyte Precursor Cells via Fyn/RhoA Signaling
复制标题
Slit2 通过 Fyn/RhoA 信号传导调节少突胶质细胞前体细胞的分散
DOI：
10.1074/jbc.m111.317610
复制
发表时间：
2012-05-18
影响因子：
4.8
通讯作者：
He, Cheng
中科院分区：
文献类型：
--
作者：
Liu, Xiujie;Lu, Yan;He, Cheng
少突胶质细胞前体细胞（Oligodendrocyte precursor cells，OPCs）是一类独特的神经胶质细胞，参与中枢神经系统的髓鞘形成。在中枢神经系统发育和修复过程中，OPC迁移对于髓鞘形成是重要的。然而，精确的细胞外和细胞内的机制，调节OPC迁移仍然难以捉摸。据报道，裂隙通过与迂回受体结合来调节神经发育过程，如迁移、粘附、轴突引导和伸长（Robos）。然而，Slits/Robos在少突胶质细胞中的潜在作用仍然未知。在这项研究中，Slit 2被发现通过Robo 1和Fyn之间的关联参与调节OPCs的分散。首先，我们研究了Robos在体外和体内OPCs中的表达。随后，Boyden小室测定显示Slit 2可以抑制OPC迁移。Robos的特异性抑制剂RoboN可以显著减弱这种作用。通过外植体迁移试验证实了这些影响。此外，用Slit 2蛋白处理OPCs使Fyn失活并增加活化的RhoA-GTP水平。最后，发现Fyn与Robo 1形成复合物，但这种关联在Slit 2刺激后减少。因此，我们首次证明Slit 2通过Fyn和RhoA信号传导调节少突胶质细胞前体细胞的分散。
Oligodendrocyte precursor cells (OPCs) are a unique type of glia that are responsible for the myelination of the central nervous system. OPC migration is important for myelin formation during central nervous system development and repair. However, the precise extracellular and intracellular mechanisms that regulate OPC migration remain elusive. Slits were reported to regulate neurodevelopmental processes such as migration, adhesion, axon guidance, and elongation through binding to roundabout receptors (Robos). However, the potential roles of Slits/Robos in oligodendrocytes remain unknown. In this study, Slit2 was found to be involved in regulating the dispersal of OPCs through the association between Robo1 and Fyn. Initially, we examined the expression of Robos in OPCs both in vitro and in vivo. Subsequently, the Boyden chamber assay showed that Slit2 could inhibit OPC migration. RoboN, a specific inhibitor of Robos, could significantly attenuate this effect. The effects were confirmed through the explant migration assay. Furthermore, treating OPCs with Slit2 protein deactivated Fyn and increased the level of activated RhoA-GTP. Finally, Fyn was found to form complexes with Robo1, but this association was decreased after Slit2 stimulation. Thus, we demonstrate for the first time that Slit2 regulates the dispersal of oligodendrocyte precursor cells through Fyn and RhoA signaling.