Promotion of axon regeneration by myelin-associated glycoprotein and Nogo through divergent signals downstream of Gi/G
Promotion of axon regeneration by myelin-associated glycoprotein and Nogo through divergent signals downstream of Gi/G
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DOI：
10.1523/jneurosci.1856-04.2004
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发表时间：
2004-07-28
影响因子：
5.3
通讯作者：
Yamashita, T
中科院分区：
文献类型：
--
作者：
Hasegawa, Y;Fujitani, M;Yamashita, T
几种髓磷脂衍生蛋白已被鉴定为CNS髓磷脂的组分，其防止成年脊椎动物CNS中的轴突再生。RhoA的激活已被证明是这些蛋白质的信号传导机制的重要组成部分。在这里，我们报告了一个额外的信号，它决定了这些蛋白质是否促进或抑制轴突生长。髓磷脂相关糖蛋白（MAG）和Nogo可能通过G（i）/G介导引起细胞内Ca ~（2+）升高和PKC激活。MAG或Nogo对神经突生长的抑制和生长锥的塌陷可以通过抑制常规PKC而转化为神经突的延伸和生长锥的扩展，但不能通过抑制肌醇1，4，5-三磷酸（IP 3）而转化。相反，MAG促进的未成熟神经元的轴突生长通过抑制IP 3而被消除。RhoA的激活不依赖于PKC。因此，PKC和IP 3之间的平衡对于髓鞘衍生蛋白双向调节轴突再生是重要的。
Several myelin-derived proteins have been identified as components of the CNS myelin that prevents axonal regeneration in the adult vertebrate CNS. Activation of RhoA has been shown to be an essential part of the signaling mechanism of these proteins. Here we report an additional signal, which determines whether these proteins promote or inhibit axon outgrowth. Myelin-associated glycoprotein (MAG) and Nogo trigger the intracellular elevation of Ca2+ as well as the activation of PKC, presumably mediated by G(i)/G. Neurite outgrowth inhibition and growth cone collapse by MAG or Nogo can be converted to neurite extension and growth cone spreading by inhibiting conventional PKC, but not by inhibiting inositol 1,4,5-triphosphate (IP3). Conversely, neurite growth of immature neurons promoted by MAG is abolished by inhibiting IP3. Activation of RhoA is independent of PKC. Thus, a balance between PKC and IP3 is important for bidirectional regulation of axon regeneration by the myelin-derived proteins.