Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Neuron. 2013 May 8;78(3):469-82. doi: 10.1016/j.neuron.2013.03.005.
Rapid action potential propagation in myelinated axons requires Na⁺ channel clustering at nodes of Ranvier. However, the mechanism of clustering at CNS nodes remains poorly understood. Here, we show that the assembly of nodes of Ranvier in the CNS involves three mechanisms: a glia-derived extracellular matrix (ECM) complex containing proteoglycans and adhesion molecules that cluster NF186, paranodal axoglial junctions that function as barriers to restrict the position of nodal proteins, and axonal cytoskeletal scaffolds (CSs) that stabilize nodal Na⁺ channels. We show that while mice with a single disrupted mechanism had mostly normal nodes, disruptions of the ECM and paranodal barrier, the ECM and CS, or the paranodal barrier and CS all lead to juvenile lethality, profound motor dysfunction, and significantly reduced Na⁺ channel clustering. Our results demonstrate that ECM, paranodal, and axonal cytoskeletal mechanisms ensure robust CNS nodal Na⁺ channel clustering.
髓鞘轴突中的快速动作电位传播需要郎飞结处的钠离子通道聚集。然而，中枢神经系统郎飞结处聚集的机制仍知之甚少。在这里，我们表明中枢神经系统中郎飞结的组装涉及三种机制：包含蛋白聚糖和黏附分子的神经胶质衍生细胞外基质（ECM）复合物，其聚集 NF186；作为限制节点蛋白位置的屏障的旁棘轴突-胶质连接；以及稳定节点钠离子通道的轴突细胞骨架支架（CS）。我们表明，虽然只有一种机制被破坏的小鼠的郎飞结大多正常，但 ECM 和旁棘屏障、ECM 和 CS 或旁棘屏障和 CS 的破坏都会导致幼年致死、严重的运动功能障碍和钠离子通道聚集显著减少。我们的结果表明，ECM、旁棘和轴突细胞骨架机制确保了中枢神经系统中强有力的郎飞结钠离子通道聚集。
