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

周围神经系统中髓鞘雪旺细胞对轴突口径的调节

• 批准号: 427278822
• 负责人: Privatdozent Dr. Hauke Werner
• 金额: --
• 依托单位: Abteilung Neurogenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/427278822?language=en
• 关键词: Regulation; axonal; calibers; myelinating; Schwann

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 Based on our unpublished observations we propose to pursue the concept that CMTM6 restricts the radial growth of myelinated axons in the PNS while it is not required for myelin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.

施万细胞对轴突进行髓鞘化，促进周围神经系统中快速、跳跃的神经传导。我们假设有髓轴突与其有髓鞘雪旺细胞在发育、形态和功能上密切相关，涉及轴突/髓磷脂界面上相关但未知的蛋白质。在一项初步实验中，我们通过生化方法富集了小鼠坐骨神经的轴突/髓磷脂界面，并将该部分进行了蛋白质组分析。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。我们将 CMTM6（趋化因子样因子 MARVEL 跨膜结构域蛋白 6）鉴定为有髓鞘雪旺细胞外轴质膜的新成分，并从基因上破坏了其表达。根据我们未发表的观察结果，我们建议追求这样的概念：CMTM6 限制 PNS 中有髓鞘轴突的径向生长，而髓鞘质生物发生本身并不是必需的。该项目将涉及生物化学/蛋白质组学、小鼠遗传学、电子显微镜以及神经传导速度和小鼠行为的评估。 Cmtm6 突变小鼠提供了一个独特的模型来检验有髓鞘雪旺细胞通过包括 CMTM6 在内的轴突表面分子限制有髓轴突的口径这一假设；这一新颖的概念将在体内进行测试。