Spy1 Protein Mediates Phosphorylation and Degradation of SCG10 Protein in Axonal Degeneration*
Spy1 Protein Mediates Phosphorylation and Degradation of SCG10 Protein in Axonal Degeneration*
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DOI：
10.1074/jbc.m114.611574
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发表时间：
2015-04
期刊：
影响因子：
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通讯作者：
Yonghua Liu;Youhua Wang;Ying Chen;Xiaohong Li;Jiao Yang;Yang Liu;A. Shen
中科院分区：
文献类型：
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作者：
Yonghua Liu;Youhua Wang;Ying Chen;Xiaohong Li;Jiao Yang;Yang Liu;A. Shen
背景：SCG 10是一种新的轴突维持因子，损伤后SCG 10的快速丢失需要JNK活性。结果：Spy 1部分以JNK依赖的方式介导SCG 10的磷酸化和降解，并调节损伤诱导的轴突变性。结论：Spy 1是SCG 10和轴突变性的重要调节因子。Spy 1可能是一种新的轴突保护治疗靶点。轴突缺失是一种广泛的神经系统疾病的破坏性后果，没有明确的机制。最近的数据表明，SCG 10是一种新的轴突维持因子，损伤后SCG 10的快速丢失需要JNK活性; JNK如何诱导SCG 10的降解尚不清楚。在这里，我们发现SCG 10是Spy 1的结合伴侣，Spy 1是Speedy/RINGO家族蛋白，参与坐骨神经损伤的细胞反应。在轴突损伤的早期阶段，Spy 1的表达与SCG 10呈负相关。Spy 1部分以JNK依赖的方式介导SCG 10的磷酸化和降解。Spy 1的抑制减弱SCG 10磷酸化和延迟损伤诱导的轴突变性。综上所述，这些数据表明Spy 1是SCG 10的重要调节因子，可以在未来的轴突保护疗法中作为靶点。
Background: SCG10 is a novel axonal maintenance factor, and rapid SCG10 loss after injury requires JNK activity. Results: Spy1 mediated SCG10 phosphorylation and degradation, partly in a JNK-dependent manner, and regulated injury-induced axonal degeneration. Conclusion: Spy1 is an important regulator of SCG10 and axon degeneration. Significance: Spy1 may be a novel axo-protective therapeutic target for axon loss. Axon loss is a destructive consequence of a wide range of neurological diseases without a clearly defined mechanism. Recent data demonstrate that SCG10 is a novel axonal maintenance factor and that rapid SCG10 loss after injury requires JNK activity; how JNK induces degradation of SCG10 is not well known. Here we showed that SCG10 was a binding partner of Spy1, a Speedy/RINGO family protein, which participated in cellular response to sciatic nerve injury. During the early stage of axonal injury, Spy1 expression was inversely correlated with SCG10. Spy1 mediated SCG10 phosphorylation and degradation partly in a JNK-dependent manner. Inhibition of Spy1 attenuated SCG10 phosphorylation and delayed injury-induced axonal degeneration. Taken together, these data suggest that Spy1 is an important regulator of SCG10 and can be targeted in future axo-protective therapeutics.