Reelin activates the small GTPase TC10 and VAMP7 to promote neurite outgrowth and regeneration of dorsal root ganglia (DRG) neurons.,Journal of Neuroscience Research

当前位置： X-MOL 学术 › J. Neurosci. Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Reelin activates the small GTPase TC10 and VAMP7 to promote neurite outgrowth and regeneration of dorsal root ganglia (DRG) neurons.
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-07-11 , DOI: 10.1002/jnr.24688
Ignacio Jausoro ₁ , Maria-Paz Marzolo ₁

Affiliation

Axonal outgrowth is a fundamental process during the development of central (CNS) and peripheral (PNS) nervous system as well as in nerve regeneration and requires accurate axonal navigation and extension to the correct target. These events need proper coordination between membrane trafficking and cytoskeletal rearrangements and are under the control of the small GTPases of the Rho family, among other molecules. Reelin, a relevant protein for CNS development and synaptic function in the adult, is also present in the PNS. Upon sciatic nerve damage, Reelin expression increases and, on the other hand, mice deficient in Reelin exhibit an impaired nerve regeneration. However, the mechanism(s) involved the Reelin‐dependent axonal growth is still poorly understood. In this work, we present evidence showing that Reelin stimulates dorsal root ganglia (DRG) regeneration after axotomy. Moreover, dissociated DRG neurons express the Reelin receptor Apolipoprotein E‐receptor 2 and also require the presence of TC10 to develop their axons. TC10 is a Rho GTPase that promotes neurite outgrowth through the exocytic fusion of vesicles at the growth cone. Here, we demonstrate for the first time that Reelin controls TC10 activation in DRG neurons. Besides, we confirmed that the known CNS Reelin target Cdc42 is also activated in DRG and controls TC10 activity. Finally, in the process of membrane addition, we found that Reelin stimulates the fusion of membrane carriers containing the v‐SNARE protein VAMP7 in vesicles that contain TC10. Altogether, our work shows a new role of Reelin in PNS, opening the option of therapeutic interventions to improve the regeneration process.

中文翻译：

Reelin 激活小 GTP 酶 TC10 和 VAMP7，促进神经突生长和背根神经节 (DRG) 神经元的再生。

轴突生长是中枢 (CNS) 和周围 (PNS) 神经系统发育以及神经再生过程中的基本过程，需要精确的轴突导航和延伸到正确的目标。这些事件需要膜运输和细胞骨架重排之间的适当协调，并且受到 Rho 家族的小 GTP 酶以及其他分子的控制。 Reelin 是成人中枢神经系统发育和突触功能的相关蛋白，也存在于三七总皂甙中。坐骨神经损伤后，Reelin 表达增加，另一方面，Reelin 缺陷的小鼠表现出神经再生受损。然而，涉及 Reelin 依赖性轴突生长的机制仍然知之甚少。在这项工作中，我们提出的证据表明，Reelin 可以刺激轴突切除后的背根神经节 (DRG) 再生。此外，分离的 DRG 神经元表达 Reelin 受体载脂蛋白 E 受体 2，并且还需要 TC10 的存在来发育轴突。 TC10 是一种 Rho GTP 酶，通过生长锥处囊泡的胞吐融合促进神经突生长。在这里，我们首次证明 Reelin 控制 DRG 神经元中的 TC10 激活。此外，我们证实已知的 CNS Reelin 靶标 Cdc42 在 DRG 中也被激活并控制 TC10 活性。最后，在膜添加过程中，我们发现Reelin刺激含有v-SNARE蛋白VAMP7的膜载体在含有TC10的囊泡中融合。总而言之，我们的工作展示了 Reelin 在 PNS 中的新作用，为改善再生过程的治疗干预提供了选择。

更新日期：2020-07-11

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11