Sorbonne Université, Inserm, CNRS, Institut du Cerveau et de la Moelle épinière, ICM-GH Pitié-Salpêtrière, Paris, France.
Assistance Publique-Hôpitaux de Paris, GH Pitié-Salpêtrière, Paris, France.
Glia. 2020 Sep;68(9):1891-1909. doi: 10.1002/glia.23812. Epub 2020 Mar 2.
In vertebrates, fast saltatory conduction along myelinated axons relies on the node of Ranvier. How nodes assemble on CNS neurons is not yet fully understood. We previously described that node-like clusters can form prior to myelin deposition in hippocampal GABAergic neurons and are associated with increased conduction velocity. Here, we used a live imaging approach to characterize the intrinsic mechanisms underlying the assembly of these clusters prior to myelination. We first demonstrated that their components can partially preassemble prior to membrane targeting and determined the molecular motors involved in their trafficking. We then demonstrated the key role of the protein β2Na for node-like clustering initiation. We further assessed the fate of these clusters when myelination proceeds. Our results shed light on the intrinsic mechanisms involved in node-like clustering prior to myelination and unravel a potential role of these clusters in node of Ranvier formation and in guiding myelination onset.
在脊椎动物中，沿着有髓轴突的快速跳跃式传导依赖于郎飞结。郎飞结如何在中枢神经系统神经元上组装尚不完全清楚。我们之前描述过，在海马 GABA 能神经元髓鞘沉积之前，可以形成类似于郎飞结的簇，并且与传导速度的增加有关。在这里，我们使用活体成像方法来描述髓鞘形成之前这些簇组装的内在机制。我们首先证明了它们的组成部分可以在膜靶向之前部分预组装，并确定了参与其运输的分子马达。然后，我们证明了蛋白 β2Na 在形成类似于郎飞结的簇中的关键作用。我们进一步评估了髓鞘形成时这些簇的命运。我们的结果阐明了髓鞘形成前形成类似于郎飞结的簇的内在机制，并揭示了这些簇在郎飞结形成和指导髓鞘起始中的潜在作用。
