Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Neuron. 2010 Feb 25;65(4):490-502. doi: 10.1016/j.neuron.2010.02.004.
Saltatory conduction requires high-density accumulation of Na(+) channels at the nodes of Ranvier. Nodal Na(+) channel clustering in the peripheral nervous system is regulated by myelinating Schwann cells through unknown mechanisms. During development, Na(+) channels are first clustered at heminodes that border each myelin segment, and later in the mature nodes that are formed by the fusion of two heminodes. Here, we show that initial clustering of Na(+) channels at heminodes requires glial NrCAM and gliomedin, as well as their axonal receptor neurofascin 186 (NF186). We further demonstrate that heminodal clustering coincides with a second, paranodal junction (PNJ)-dependent mechanism that allows Na(+) channels to accumulate at mature nodes by restricting their distribution between two growing myelin internodes. We propose that Schwann cells assemble the nodes of Ranvier by capturing Na(+) channels at heminodes and by constraining their distribution to the nodal gap. Together, these two cooperating mechanisms ensure fast and efficient conduction in myelinated nerves.
跳跃传导需要在郎飞结处高密度积聚钠离子通道。周围神经系统中的郎飞结钠离子通道簇集是由少突胶质细胞通过未知的机制调节的。在发育过程中，钠离子通道首先在每个髓鞘节的边缘聚集形成半结，然后在由两个半结融合形成的成熟结处聚集。在这里，我们表明钠离子通道在半结处的初始聚集需要神经胶质细胞 NrCAM 和 gliomedin，以及它们的轴突受体神经束蛋白 186（NF186）。我们进一步证明，半结聚集与第二个、连接结（PNJ）依赖性机制同时发生，该机制通过限制钠离子通道在两个生长中的髓鞘节间的分布，使钠离子通道能够在成熟的结处积聚。我们提出，少突胶质细胞通过在半结处捕获钠离子通道，并将其分布限制在结区，从而组装郎飞结。这两个协同作用的机制共同确保了有髓神经的快速和有效的传导。
