Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling.
Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling.
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DOI：
10.1177/1759091415602859
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发表时间：
2015-09
期刊：
影响因子：
4.7
通讯作者：
Laursen LS
中科院分区：
文献类型：
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作者：
Linneberg C;Harboe M;Laursen LS
在中枢神经系统中，轴突的髓鞘形成是确保快速跳跃传导和神经元存活所必需的。然而，并不是所有的轴突都有髓鞘，并且参与引导少突胶质细胞朝向轴突髓鞘化的分子机制还没有很好地理解。在髓鞘形成之前，只有少数参与调节轴神经胶质相互作用的负或正指导线索已被确定。一个例子是层粘连蛋白，已知其是早期轴突-神经胶质相互作用所需的，其通过α6β1整联蛋白发挥作用。在这里，我们确定了Eph-肝配蛋白家族的指导受体作为新的监管机构的初始轴神经胶质细胞的相互作用，髓鞘形成之前。我们证明，所谓的正向和反向信号，Eph和ephrin亚家族的成员介导的，有不同的和相反的影响过程的延伸和髓鞘片的形成。EphA正向信号传导抑制少突胶质细胞突起延伸和髓鞘片形成，并且阻断通过该受体的双向信号传导增强髓鞘形成。类似地，EphB正向信号传导也减少髓鞘膜形成，但与EphA正向信号传导相反，这以整联蛋白依赖性方式发生，其可以通过组成型活性β1-整联蛋白的过表达来逆转。此外，由EphA 4或EphB 1诱导的肝配蛋白-B反向信号传导增强髓鞘片层形成。结合，这表明Eph-ephrin受体是轴突和少突胶质细胞之间双向信号传导的重要介质。这进一步暗示平衡Eph-ephrin正向和反向信号传导在选择要有髓鞘的轴突的过程中是重要的。
In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.