Three mechanisms assemble central nervous system nodes of Ranvier.

Three mechanisms assemble central nervous system nodes of Ranvier.
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DOI:
10.1016/j.neuron.2013.03.005
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发表时间:
2013-05-08
期刊:
影响因子:
16.2
通讯作者:
Rasband MN
Rasband MN
中科院分区:
医学1区
文献类型:
--
作者:
Susuki K;Chang KJ;Zollinger DR;Liu Y;Ogawa Y;Eshed-Eisenbach Y;Dours-Zimmermann MT;Oses-Prieto JA;Burlingame AL;Seidenbecher CI;Zimmermann DR;Oohashi T;Peles E;Rasband MN

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有髓轴突中动作电位的快速传播需要 Na+ 通道在 Ranvier 节点处聚集。然而,中枢神经系统节点的聚类机制仍然知之甚少。在这里,我们发现中枢神经系统中郎飞叶节点的组装涉及三种机制:神经胶质细胞衍生的细胞外基质(ECM)复合物,含有聚集NF186的蛋白聚糖和粘附分子,作为限制节点蛋白位置的屏障的节点旁轴胶质连接,以及稳定节点Na+通道的轴突细胞骨架支架(CS)。我们发现,虽然具有单一机制破坏的小鼠大多具有正常的节点,但 ECM 和节旁屏障、ECM 和 CS 或节旁屏障和 CS 的破坏都会导致幼年死亡、严重的运动功能障碍以及 Na+ 通道聚集的显着减少。我们的结果表明,ECM、节点旁和轴突细胞骨架机制确保了稳健的 CNS 节点 Na+ 通道聚类。
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.
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