Neurofascin and Kv7.3 are delivered to somatic and axon terminal surface membranes en route to the axon initial segment.
Neurofascin and Kv7.3 are delivered to somatic and axon terminal surface membranes en route to the axon initial segment.
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DOI：
10.7554/elife.60619
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发表时间：
2020-09-09
期刊：
影响因子：
7.7
通讯作者：
Brophy PJ
中科院分区：
文献类型：
--
作者：
Ghosh A;Malavasi EL;Sherman DL;Brophy PJ
离子通道复合物促进在哺乳动物轴突起始段（AIS）的动作电位起始，并且通过蛋白质的募集或损失调节AIS大小可以影响神经元兴奋性。虽然内吞作用有助于AIS营业额，如何膜蛋白交通到这个近端轴突域是不完全了解。Neurosfascin186（Nfas186）在稳定AIS复合物至近端轴突中具有重要作用，并且AIS通道蛋白Kv7.3调节神经元兴奋性。因此，我们研究了这些蛋白质如何到达AIS。囊泡将Nfas186转运到索马和轴突末端，在那里它们与神经元质膜融合。Nfas186在插入轴突膜后是高度移动的，并且双向扩散，直到通过其与AnkaloG的相互作用固定在AIS处。Kv7.3也同样被招募到AIS。这项研究揭示了关键蛋白质是如何传递到AIS的，从而它们如何有助于其功能可塑性。
Ion channel complexes promote action potential initiation at the mammalian axon initial segment (AIS), and modulation of AIS size by recruitment or loss of proteins can influence neuron excitability. Although endocytosis contributes to AIS turnover, how membrane proteins traffic to this proximal axonal domain is incompletely understood. Neurofascin186 (Nfasc186) has an essential role in stabilising the AIS complex to the proximal axon, and the AIS channel protein Kv7.3 regulates neuron excitability. Therefore, we have studied how these proteins reach the AIS. Vesicles transport Nfasc186 to the soma and axon terminal where they fuse with the neuronal plasma membrane. Nfasc186 is highly mobile after insertion in the axonal membrane and diffuses bidirectionally until immobilised at the AIS through its interaction with AnkyrinG. Kv7.3 is similarly recruited to the AIS. This study reveals how key proteins are delivered to the AIS and thereby how they may contribute to its functional plasticity.