Preferential targeting of Nav1.6 voltage-gated Na+ Channels to the axon initial segment during development.
Preferential targeting of Nav1.6 voltage-gated Na+ Channels to the axon initial segment during development.
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DOI：
10.1371/journal.pone.0124397
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tamkun MM
中科院分区：
文献类型：
--
作者：
Akin EJ;Solé L;Dib-Hajj SD;Waxman SG;Tamkun MM
在轴突成熟过程中，电压门控钠 (Nav) 通道在轴突起始段 (AIS) 处以高浓度积累。这种定位对于有效启动动作电位是必要的。由于缺乏适合对特定位于细胞表面的通道进行高分辨率成像的 Nav 试剂，轴突发育过程中通道运输至 AIS 的机制仍然难以捉摸。使用光学脉冲追踪方法与包含细胞外生物素化结构域的新型 Nav1.6 构建体相结合，我们证明 Nav1.6 通道在神经元发育过程中通过直接囊泡运输优先插入 AIS 膜。单分子追踪表明，轴突通道在递送后立即固定，而递送到胞体的通道通常是移动的。缺乏锚蛋白结合基序的 Nav1.6 通道和包含 Nav 锚蛋白结合结构域的嵌合 Kv2.1 通道均未显示优先 AIS 插入。这些数据共同支持了一个模型，其中需要锚蛋白结合才能优先将 Nav1.6 插入到 AIS 质膜中。相反，单独的锚蛋白G结合并不能将蛋白质优先递送至AIS。
During axonal maturation, voltage-gated sodium (Nav) channels accumulate at the axon initial segment (AIS) at high concentrations. This localization is necessary for the efficient initiation of action potentials. The mechanisms underlying channel trafficking to the AIS during axonal development have remained elusive due to a lack of Nav reagents suitable for high resolution imaging of channels located specifically on the cell surface. Using an optical pulse-chase approach in combination with a novel Nav1.6 construct containing an extracellular biotinylation domain we demonstrate that Nav1.6 channels are preferentially inserted into the AIS membrane during neuronal development via direct vesicular trafficking. Single-molecule tracking illustrates that axonal channels are immediately immobilized following delivery, while channels delivered to the soma are often mobile. Neither a Nav1.6 channel lacking the ankyrin-binding motif nor a chimeric Kv2.1 channel containing the Nav ankyrinG-binding domain show preferential AIS insertion. Together these data support a model where ankyrinG-binding is required for preferential Nav1.6 insertion into the AIS plasma membrane. In contrast, ankyrinG-binding alone does not confer the preferential delivery of proteins to the AIS.
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DOI：
10.1083/jcb.200805169
发表时间：
2008-12-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bréchet A;Fache MP;Brachet A;Ferracci G;Baude A;Irondelle M;Pereira S;Leterrier C;Dargent B
通讯作者：
Dargent B
影响因子：
3.3
作者：
Deutsch E;Weigel AV;Akin EJ;Fox P;Hansen G;Haberkorn CJ;Loftus R;Krapf D;Tamkun MM
通讯作者：
Tamkun MM
影响因子：
64.5
作者：
Galiano MR;Jha S;Ho TS;Zhang C;Ogawa Y;Chang KJ;Stankewich MC;Mohler PJ;Rasband MN
通讯作者：
Rasband MN
影响因子：
48
作者：
Chen, I;Howarth, M;Ting, AY
通讯作者：
Ting, AY
DOI：
10.1016/s0169-328x(96)00241-0
发表时间：
1997-04-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Felts, PA;Yokoyama, S;Waxman, SG
通讯作者：
Waxman, SG