Regulation of axonal calibers by myelinating Schwann cells in the peripheral nervous system

周围神经系统中的快速、跳跃式神经传导由许旺细胞的轴突髓鞘形成促进。我们推测，密切的发展，形态和功能的有髓轴突与髓鞘雪旺氏细胞的协会涉及相关的，但未知的蛋白质在轴突/髓鞘界面。在一个试点实验中，我们生物化学富集的轴突/髓鞘界面的小鼠坐骨神经，并将这部分蛋白质组分析。为了选择蛋白质进行更详细的表征，我们评估了可能参与细胞间信号传导的蛋白质的数据集。我们确定CMTM 6（趋化因子样MARVEL跨膜结构域蛋白6）作为一种新的组成部分的髓鞘形成雪旺细胞的近轴质膜和遗传破坏其表达。基于我们未发表的观察结果，我们提出了以下概念：CMTM 6限制PNS中有髓鞘轴突的径向生长，而它本身并不是髓鞘生物发生所必需的。该项目将涉及生物化学/蛋白质组学，小鼠遗传学，电子显微镜，神经传导速度和小鼠行为的评估。Cmtm 6突变小鼠提供了一个独特的模型来测试的假设，髓鞘形成的雪旺细胞限制口径的有髓轴突通过包括CMTM 6的近轴表面分子，这一新的概念将在体内进行测试。

Rapid, saltatory nerve conduction in the peripheral nervous system is facilitated by the myelination of axons by Schwann cells. We hypothesize that the close developmental, morphological and functional association of myelinated axons with their myelinating Schwann cells involves relevant, but yet unknown proteins at the axon/myelin-interface. In a pilot experiment we biochemically enriched the axon/myelin-interface of mouse sciatic nerves and subjected this fraction to proteome analysis. To select proteins for more detailed characterization, we evaluated our dataset for proteins that are probably involved in cell-to-cell signaling. We identified CMTM6 (chemokine-like factor-like MARVEL-transmembrane domain-containing protein 6) as a novel constituent of the adaxonal plasma membrane of myelinating Schwann cells and genetically disrupted its expression. Based on our unpublished observations we propose to pursue the concept that CMTM6 restricts the radial growth of myelinated axons in the PNS while it is not required for myelin biogenesis per se. This project will involve biochemistry/proteomics, mouse genetics, electron microscopy, and assessment of nerve conduction velocity and mouse behavior. Cmtm6-mutant mice provide a unique model to test the hypothesis that myelinating Schwann cells restrict the calibers of myelinated axons via adaxonal surface molecules including CMTM6; this novel concept will be tested in vivo.