AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing.
AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing.
复制标题
在轴突初始段和正常动作电势射击处的电压门控Na通道的聚类是必需的。
DOI：
10.1083/jcb.143.5.1295
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发表时间：
1998-11-30
影响因子：
7.8
通讯作者：
Bennett, V
中科院分区：
文献类型：
--
作者：
Zhou, D;Lambert, S;Malen, P L;Carpenter, S;Boland, L M;Bennett, V
电压门控性钠通道(NACH)与膜骨架蛋白ankyrinG的异构体共同定位于哺乳动物神经肌肉接头的轴突起始段、Ranvier结节和突触后折叠。通过区域特异性敲除小鼠小脑中的ankyrinG来评价ankyrinG在引导NACH定位到轴突起始节段中的作用。突变小鼠在出生后16天左右表现出进行性共济失调，随后浦肯野神经元丢失。在突变的小鼠小脑中，颗粒细胞神经元的轴突起始段缺乏NACH，浦肯野细胞缺乏启动动作电位和支持快速重复放电的能力。神经束素是L1CAM家族中的一员，属于黏附蛋白结合的细胞黏附分子家族，也表现出浦肯野细胞神经元起始节的定位受损。这些结果表明，ankyrinG是聚集在轴突起始段的NACH和神经束素所必需的，也是生理水平的钠通道活动所必需的。
Voltage-gated sodium channels (NaCh) are colocalized with isoforms of the membrane-skeletal protein ankyrinG at axon initial segments, nodes of Ranvier, and postsynaptic folds of the mammalian neuromuscular junction. The role of ankyrinG in directing NaCh localization to axon initial segments was evaluated by region-specific knockout of ankyrinG in the mouse cerebellum. Mutant mice exhibited a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons. In mutant mouse cerebella, NaCh were absent from axon initial segments of granule cell neurons, and Purkinje cells showed deficiencies in their ability to initiate action potentials and support rapid, repetitive firing. Neurofascin, a member of the L1CAM family of ankyrin-binding cell adhesion molecules, also exhibited impaired localization to initial segments of Purkinje cell neurons. These results demonstrate that ankyrinG is essential for clustering NaCh and neurofascin at axon initial segments and is required for physiological levels of sodium channel activity.