Sherman Diane L, Tait Steven, Melrose Shona, Johnson Richard, Zonta Barbara, Court Felipe A, Macklin Wendy B, Meek Stephen, Smith Andrew J H, Cottrell David F, Brophy Peter J
Centre for Neuroscience Research, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom.
Neuron. 2005 Dec 8;48(5):737-42. doi: 10.1016/j.neuron.2005.10.019.
Voltage-gated sodium channels are concentrated in myelinated nerves at the nodes of Ranvier flanked by paranodal axoglial junctions. Establishment of these essential nodal and paranodal domains is determined by myelin-forming glia, but the mechanisms are not clear. Here, we show that two isoforms of Neurofascin, Nfasc155 in glia and Nfasc186 in neurons, are required for the assembly of these specialized domains. In Neurofascin-null mice, neither paranodal adhesion junctions nor nodal complexes are formed. Transgenic expression of Nfasc155 in the myelinating glia of Nfasc-/- nerves rescues the axoglial adhesion complex by recruiting the axonal proteins Caspr and Contactin to the paranodes. However, in the absence of Nfasc186, sodium channels remain diffusely distributed along the axon. Our study shows that the two major Neurofascins play essential roles in assembling the nodal and paranodal domains of myelinated axons; therefore, they are essential for the transition to saltatory conduction in developing vertebrate nerves.
电压门控钠通道集中在郎飞结处的有髓神经中，郎飞结两侧为结旁轴突-胶质连接。这些重要的结区和结旁区的形成由形成髓鞘的胶质细胞决定，但具体机制尚不清楚。在这里，我们表明神经束蛋白的两种异构体，即胶质细胞中的Nfasc155和神经元中的Nfasc186，是这些特殊区域组装所必需的。在神经束蛋白缺失的小鼠中，既不形成结旁黏附连接也不形成结复合体。在Nfasc-/-神经的髓鞘形成胶质细胞中，Nfasc155的转基因表达通过将轴突蛋白Caspr和Contactin募集到结旁来挽救轴突-胶质黏附复合体。然而，在没有Nfasc186的情况下，钠通道仍沿轴突呈弥散分布。我们的研究表明，两种主要的神经束蛋白在组装有髓轴突的结区和结旁区中起重要作用；因此，它们对于发育中的脊椎动物神经向跳跃式传导的转变至关重要。
