Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK.
Neuron. 2011 Mar 10;69(5):945-56. doi: 10.1016/j.neuron.2011.02.021.
The axon initial segment (AIS) is critical for the initiation and propagation of action potentials. Assembly of the AIS requires interactions between scaffolding molecules and voltage-gated sodium channels, but the molecular mechanisms that stabilize the AIS are poorly understood. The neuronal isoform of Neurofascin, Nfasc186, clusters voltage-gated sodium channels at nodes of Ranvier in myelinated nerves: here, we investigate its role in AIS assembly and stabilization. Inactivation of the Nfasc gene in cerebellar Purkinje cells of adult mice causes rapid loss of Nfasc186 from the AIS but not from nodes of Ranvier. This causes AIS disintegration, impairment of motor learning and the abolition of the spontaneous tonic discharge typical of Purkinje cells. Nevertheless, action potentials with a modified waveform can still be evoked and basic motor abilities remain intact. We propose that Nfasc186 optimizes communication between mature neurons by anchoring the key elements of the adult AIS complex.
轴突起始段（AIS）对于动作电位的起始和传播至关重要。AIS 的组装需要支架分子和电压门控钠离子通道之间的相互作用，但稳定 AIS 的分子机制还知之甚少。神经型神经束蛋白（Neurofascin）的神经元同工型 Nfasc186 在有髓神经的郎飞结处聚集电压门控钠离子通道：在这里，我们研究其在 AIS 组装和稳定中的作用。成年小鼠小脑浦肯野细胞中 Nfasc 基因的失活导致 AIS 中 Nfasc186 的快速丢失，但郎飞结处不会丢失。这会导致 AIS 解体、运动学习受损以及浦肯野细胞的自发紧张放电消失。尽管如此，仍可以激发具有修改后的波形的动作电位，并且基本运动能力保持完整。我们提出，Nfasc186 通过锚定成年 AIS 复合物的关键元素，优化成熟神经元之间的通讯。
