Differential Stability of PNS and CNS Nodal Complexes When Neuronal Neurofascin Is Lost

作者：Desmazieres Anne; Zonta Barbara; Zhang Ao; Wu Lai Man N; Sherman Diane L; Brophy Peter J^*

来源：Journal of Neuroscience, 2014, 34(15): 5083-5088.

DOI：10.1523/JNEUROSCI.4662-13.2014

• neurofascin
• nodes of Ranvier
• sodium channels
• myelination

Fast, saltatory conduction in myelinated nerves requires the clustering of voltage-gated sodium channels (Nav) at nodes of Ranvier in a nodal complex. The Neurofascin (Nfasc) gene encodes neuronal Neurofascin 186 (Nfasc186) at the node and glial Neurofascin 155 at the paranode, and these proteins play a key role in node assembly. However, their role in the maintenance and stability of the node is less well understood. Here we show that by inducible ablation of Nfasc in neurons in adult mice, Nfasc186 expression is reduced by > 99% and94% at PNS and CNS nodes, respectively. Gliomedin and NrCAM at PNS and brevican at CNS nodes are largely lost with neuronal neurofascin; however, Nav at nodes of Ranvier persist, albeit with similar to 40% reduction in expression levels. beta IV Spectrin, ankyrin G, and, to a lesser extent, the beta 1 subunit of the sodium channel, are less affected at the PNS node than in the CNS. Nevertheless, there is a 38% reduction in PNS conduction velocity. Loss of Nfasc186 provokes CNS paranodal disorganization, but this does not contribute to loss of Nav. These results show that Nav at PNSnodes are still maintained in a nodal complex when neuronal neurofascin is depleted, whereas the retention of nodal Nav in the CNS, despite more extensive dissolution of the complex, suggests a supportive role for the partially disrupted paranodal axoglial junction in selectively maintaining Nav at the CNS node.

• 出版日期2014-4-9