Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons.
Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons.
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DOI：
10.7554/elife.68089
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发表时间：
2021-07-09
期刊：
影响因子：
7.7
通讯作者：
Brophy PJ
中科院分区：
文献类型：
--
作者：
Malavasi EL;Ghosh A;Booth DG;Zagnoni M;Sherman DL;Brophy PJ
电压门控钠通道在脊椎动物神经中聚集在郎维氏结处的大分子复合物中以促进快速神经冲动传导。周围神经中的节点组装被认为起始于髓鞘化雪旺细胞末端的半节点，并且半节点的融合导致节点的建立。在这里，我们表明，组装的“早期集群”的节点蛋白在小鼠轴突膜前半结形成。神经成束蛋白（Nfasc）是节点组装所必需的，早期簇的形成也需要神经元Nfasc。早期的簇是移动的，并且它们的蛋白质通过横向扩散动态地募集。它们不仅可以相互融合，也可以与半突融合，从而有助于外周轴突中节点的发育。早期集群的形成构成了外周节点组装的最早阶段，并扩展了建立这些基本结构的策略。
Voltage-gated sodium channels cluster in macromolecular complexes at nodes of Ranvier to promote rapid nerve impulse conduction in vertebrate nerves. Node assembly in peripheral nerves is thought to be initiated at heminodes at the extremities of myelinating Schwann cells, and fusion of heminodes results in the establishment of nodes. Here we show that assembly of ‘early clusters’ of nodal proteins in the murine axonal membrane precedes heminode formation. The neurofascin (Nfasc) proteins are essential for node assembly, and the formation of early clusters also requires neuronal Nfasc. Early clusters are mobile and their proteins are dynamically recruited by lateral diffusion. They can undergo fusion not only with each other but also with heminodes, thus contributing to the development of nodes in peripheral axons. The formation of early clusters constitutes the earliest stage in peripheral node assembly and expands the repertoire of strategies that have evolved to establish these essential structures.