Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Electron Microscopy Core Unit, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Elife. 2022 Mar 11;11:e75523. doi: 10.7554/eLife.75523.
Oligodendrocytes facilitate rapid impulse propagation along the axons they myelinate and support their long-term integrity. However, the functional relevance of many myelin proteins has remained unknown. Here, we find that expression of the tetraspan-transmembrane protein CMTM5 (chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) is highly enriched in oligodendrocytes and central nervous system (CNS) myelin. Genetic disruption of the gene in oligodendrocytes of mice does not impair the development or ultrastructure of CNS myelin. However, oligodendroglial deficiency causes an early-onset progressive axonopathy, which we also observe in global and tamoxifen-induced oligodendroglial mutants. Presence of the mutation ameliorates the axonopathy, implying a Wallerian degeneration-like pathomechanism. These results indicate that CMTM5 is involved in the function of oligodendrocytes to maintain axonal integrity rather than myelin biogenesis.
少突胶质细胞促进其髓鞘化的轴突的快速冲动传递，并支持其长期完整性。然而，许多髓鞘蛋白的功能相关性仍然未知。在这里，我们发现四跨膜蛋白 CMTM5（趋化因子样因子样 MARVEL 跨膜结构域包含蛋白 5）的表达在少突胶质细胞和中枢神经系统（CNS）髓鞘中高度富集。在小鼠的少突胶质细胞中敲除 基因不会损害 CNS 髓鞘的发育或超微结构。然而，少突胶质细胞缺失导致早发性进行性轴突病，我们也在全局和他莫昔芬诱导的少突胶质细胞 突变体中观察到这种情况。存在 突变可改善轴突病，表明存在 Wallerian 变性样发病机制。这些结果表明 CMTM5 参与少突胶质细胞的功能以维持轴突完整性，而不是髓鞘发生。
