Concentration of neddylation-related molecules in paranodal myelin of the peripheral nervous system.
Concentration of neddylation-related molecules in paranodal myelin of the peripheral nervous system.
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DOI：
10.2183/pjab.92.56
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Baba H
中科院分区：
文献类型：
--
作者：
Kajigaya H;Ishibashi T;Hayashi A;Yamaguchi Y;Baba H
去甲基化是一种可逆的翻译后修饰，在这种修饰中，一种名为NEDD8的类似泛素的小分子与底物蛋白质共价结合。尽管最近的一项研究表明，去核化对于大脑中树突棘的形成和维持是必不可少的，但这种蛋白质修饰在周围神经中的作用完全不清楚。在本研究中，除了有髓鞘和无髓鞘雪旺细胞体外，NEDD8和DCUN1D2(剔除缺失1，结构域2)分子也集中在外周髓鞘的副阳极处。这些蛋白质主要定位在较大的纤维中，而不是较小直径的纤维中。发育分析表明，这些分子最早出现在髓鞘形成的后期，这种特征分布在硫脂缺乏的小鼠中消失了，在节点旁轴突-神经胶质连接被破坏的小鼠中，这一特征的分布消失了。这些结果表明，髓鞘旁阳极可能是周围神经发生变性的区域之一。
Neddylation is a reversible post-translational modification in which a small ubiquitin-like molecule called NEDD8 covalently binds to substrate proteins. Although a recent study suggests that neddylation is essential for formation and maintenance of dendritic spines in the brain, the role of this protein modification in the peripheral nerves is wholly unknown. In this study, we demonstrate that neddylation-related molecules, NEDD8 and DCUN1D2 (defective in cullin neddylation 1, domain containing 2), were concentrated at the paranode of peripheral myelin, in addition to the myelinated and unmyelinated Schwann cell bodies. These proteins were localized mainly within larger fibers, but not in fibers with small diameters. Developmental analyses showed that these molecules first appeared at the paranode during later stages of myelination, and this characteristic distribution disappeared in sulfatide-deficient mice in which paranodal axo-glial junctions were disrupted. These results suggest that the myelin paranode may be one of the regions where neddylation occurs within the peripheral nerves.