Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion
Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion
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DOI：
10.1073/pnas.042601799
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发表时间：
2002-02-19
影响因子：
11.1
通讯作者：
Bennett, V
中科院分区：
文献类型：
--
作者：
Jenkins, SM;Bennett, V
兰维尔结节是轴突细胞膜上高度富含传播动作电位的电压门控钠通道的可兴奋区域。蛋白质在节点聚集的机制一直是争议的来源。在本研究中，对视神经轴突Ranvier结节的发育分析表明，早期结节中间产物是由ankyrin-G定义的。其他节点成分，包括βIV血影蛋白、电压门控钠通道和L1细胞黏附分子神经筋膜蛋白，随后被招募到Ankyrin-G聚集点。在髓鞘功能障碍小鼠突变体jimpy中，研究了完整的副阳离子在蛋白质聚集中的作用。Jimpy小鼠没有完整的结旁轴突接触，这表明在副结节内完全缺乏Neuresin/Conactin相关蛋白/Paranodin聚集。在没有完整的副阳极的情况下，ankyrin-G仍然能够聚集，尽管在小的视神经中可以看到比野生类型的视神经中更少的ankyrin聚集。在幼鼠中，Na(V)1.2、Na(V)1.6、βIV血影蛋白和神经束蛋白在ankyrin-G聚集部位的募集没有受到损害，这表明结节的形成不依赖于完整的结旁轴突接触。
Nodes of Ranvier are excitable regions of axonal membranes highly enriched in voltage-gated sodium channels that propagate action potentials. The mechanism of protein clustering at nodes has been a source of controversy. In this study, developmental analysis of nodes of Ranvier in optic nerve axons reveals that early node intermediates are defined by ankyrin-G. Other node components, including beta IV spectrin, voltage-gated sodium channels, and the L1 cell adhesion molecule neurofascin, are subsequently recruited to sites of ankyrin-G clustering. The role of intact paranodes in protein clustering was examined in the dysmyelinating mouse mutant jimpy. Jimpy mice do not have intact paranodal axoglial contacts, which is indicated by a complete lack of neurexin/contactin-associated protein/paranodin clustering in paranodes. In the absence of intact paranodes, ankyrin-G was still able to cluster, although fewer ankyrin clusters were seen in jimpy optic nerves than in wild-type optic nerves. Recruitment of Na(v)1.2, Na(v)1.6, beta IV spectrin, and neurofascin to sites of ankyrin-G clustering is unimpaired in jimpy mice, indicating that node formation occurs independent of intact paranodal axoglial contacts.