Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier

Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier
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DOI:
10.1016/j.neuron.2005.06.026
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发表时间:
2005-07-21
期刊:
影响因子:
16.2
通讯作者:
Peles, E
Peles, E
中科院分区:
医学1区
文献类型:
--
作者:
Eshed, Y;Feinberg, K;Peles, E

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Na+通道在郎维尔结的积聚是跳跃传导的先决条件。在周围神经中,这些通道沿着轴膜的聚集通过一种未知的机制由髓鞘形成的Schwarm细胞调节。我们报告的鉴定gliomedin,神经成束蛋白和NrCAM,两个轴突免疫球蛋白细胞粘附分子,与Na+通道在节点的朗维尔神经胶质配体。神经胶质介导蛋白由髓鞘形成的雪旺细胞表达,并在发育过程中积累在每个髓鞘节段的边缘,在那里它与形成节点对齐。通过RNAi消除胶质细胞调节素的表达,或向髓鞘形成培养物中加入神经成束蛋白的可溶性细胞外结构域,这引起胶质细胞调节素沿沿着的重新分布,从而消除了节点形成。此外,可溶性神经胶质细胞介导的神经胶质细胞样集群的Na+通道的施瓦尔细胞的情况下。我们建议,gliomedin提供了一个神经胶质的朗维尔周边节点的形成线索。
Accumulation of Na+ channels at the nodes of Ranvier is a prerequisite for saltatory conduction. In peripheral nerves, clustering of these channels along the axolemma is regulated by myelinating Schwarm cells through a yet unknown mechanism. We report the identification of gliomedin, a glial ligand for neurofascin and NrCAM, two axonal immunoglobulin cell adhesion molecules that are associated with Na+ channels at the nodes of Ranvier. Gliomedin is expressed by myelinating Schwann cells and accumulates at the edges of each myelin segment during development, where it aligns with the forming nodes. Eliminating the expression of gliomedin by RNAi, or the addition of a soluble extracellular domain of neurofascin to myelinating cultures, which caused the redistribution of gliomedin along the internodes, abolished node formation. Furthermore, a soluble gliomedin induced nodal-like clusters of Na+ channels in the absence of Schwarm cells. We propose that gliomedin provides a glial cue for the formation of peripheral nodes of Ranvier.