The T1 domain of Kv1.3 mediates intracellular targeting to axons.
The T1 domain of Kv1.3 mediates intracellular targeting to axons.
复制标题
Kv1.3 的 T1 结构域介导细胞内对轴突的靶向。
DOI：
10.1111/j.1460-9568.2005.04384.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Arnold,DonB
中科院分区：
文献类型：
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作者：
Rivera,JacquelineF;Chu,Po-Ju;Arnold,DonB
激振K+通道在调节轴突电兴奋性中起重要作用。最近的研究表明，Kv1.2的T1四聚域对于将通道靶向到轴突表面既是必要的也是充分的[Gu， C., Jan， Y.N. & Jan， L.Y. (2003)Science, 301,646-649]。在这里，我们使用相关通道Kv1.3作为模型来研究介导轴突靶向的细胞机制。我们发现Kv1.3的T1结构域是必要和充分的，以介导通道的轴突表面的锥体神经元皮层片。T1结构域也足以引起细胞内蛋白的优先轴突定位，这表明该结构域可能不通过室特异性内吞作用或室特异性囊泡对接起作用。为了确定T1结构域是否介导转运囊泡的轴突运输，我们比较了活皮层神经元中含有绿色荧光蛋白标记的转铁蛋白受体的囊泡的运输与含有与T1结构域融合的相同蛋白的囊泡的运输。与先前发表的结果一致，含有野生型转铁蛋白受体的囊泡不会运输到轴突；然而，那些含有与T1融合的转铁蛋白受体的细胞确实向轴突运输。这些结果与Kv1.3的T1结构域通过引起运输囊泡向轴突运输而介导轴突靶向一致，并且它们代表了这种机制可能是轴突靶向的第一个证据。
Shaker K+channels play an important role in modulating electrical excitability of axons. Recent work has demonstrated that the T1 tetramerization domain of Kv1.2 is both necessary and sufficient for targeting of the channel to the axonal surface [Gu, C., Jan, Y.N. & Jan, L.Y. (2003)Science,301,646–649]. Here we use a related channel, Kv1.3, as a model to investigate cellular mechanisms that mediate axonal targeting. We show that the T1 domain of Kv1.3 is necessary and sufficient to mediate targeting of the channel to the axonal surface in pyramidal neurons in slices of cortex from neonatal rat. The T1 domain is also sufficient to cause preferential axonal localization of intracellular protein, which indicates that the domain probably does not work through compartment‐specific endocytosis or compartment‐specific vesicle docking. To determine whether the T1 domain mediates axonal trafficking of transport vesicles, we compared the trafficking of vesicles containing green fluorescent protein‐labelled transferrin receptor with those containing the same protein fused with the T1 domain in living cortical neurons. Vesicles containing the wild‐type transferrin receptor did not traffic to the axon, in accord with previously published results; however, those containing the transferrin receptor fused to T1 did traffic to the axon. These results are consistent with the T1 domain of Kv1.3 mediating axonal targeting by causing transport vesicles to traffic to axons and they represent the first evidence that such a mechanism might underlie axonal targeting.