Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration.
Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration.
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肌动蛋白聚合对于沃勒利变性期间的髓鞘片段化至关重要。
DOI：
10.1523/jneurosci.4537-10.2011
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发表时间：
2011-02-09
期刊：
影响因子：
--
通讯作者：
Park HT
中科院分区：
文献类型：
--
作者：
Jung J;Cai W;Lee HK;Pellegatta M;Shin YK;Jang SY;Suh DJ;Wrabetz L;Feltri ML;Park HT
周围神经损伤后发生沃勒变性（Wallerian degeneration，WD）的机制尚不清楚。在WD的早期，髓鞘分裂成卵圆形结构发生在施密特-兰特曼切口（SLI）附近，这是髓鞘的一个非致密区域，含有典型的粘附连接。在这项研究中，我们发现，新的F-肌动蛋白聚合发生在SLI的小鼠坐骨神经损伤后，它的抑制不仅阻止了降解的E-钙粘蛋白的SLI，但也髓鞘卵形体的形成。然而，肌动蛋白聚合的抑制不能阻止雪旺细胞的去分化。在损伤神经的远端残端观察到Rac GT3的激活，并且特异性Rac抑制剂，显性负Rac和Rac 1-RNAi阻断髓鞘卵形体的形成。总之，这些研究结果表明，肌动蛋白在SLI的动态变化是必不可少的启动脱髓鞘周围神经损伤后。
The mechanisms that trigger Wallerian degeneration (WD) of peripheral nerves after injury are not well understood. During the early period of WD, fragmentation of myelin into ovoid structures occurs near the Schmidt-Lantermann incisures (SLI), a noncompact region of the myelin sheath containing autotypical adherens junction. In this study, we found that new F-actin polymerization occurs in the SLI of mouse sciatic nerves after injury and that its inhibition prevented not only the degradation of E-cadherin in the SLI but also myelin ovoid formation. However, the inhibition of actin polymerization could not block Schwann cell dedifferentiation. The activation of Rac GTPase was observed in the distal stump of the injured nerves, and a specific Rac inhibitor, a dominant negative Rac and Rac1-RNAi blocked myelin ovoid formation. Together, these findings suggest that dynamic changes in actin in the SLI are essential for initiation of demyelination after peripheral nerve injury.