Specific Sorting and Post-Golgi Trafficking of Dendritic Potassium Channels in Living Neurons
Specific Sorting and Post-Golgi Trafficking of Dendritic Potassium Channels in Living Neurons
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DOI：
10.1074/jbc.m113.534495
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发表时间：
2014-04-11
影响因子：
4.8
通讯作者：
Misonou, Hiroaki
中科院分区：
文献类型：
--
作者：
Jensen, Camilla Stampe;Watanabe, Shoji;Misonou, Hiroaki
背景：电压门控性K+通道定位于神经元的特定树突亚区室，调节树突的兴奋性。结果：树突状细胞Kv通道在不同的高尔基体后转运囊泡群体中进行分类和运输。结论：Kv通道的分类及其随后通过独特机制的运输对于它们在树突内的特定定位至关重要。重要性：我们的研究揭示了树突状细胞离子通道存在新的亚区室特异性运输途径，离子通道的正确膜定位对神经细胞的功能至关重要。特别地，树突的计算能力取决于特定子隔室中不同离子通道的定位。然而，控制离子通道定位在不同的树突状亚室的分子机制在很大程度上是未知的。在这里，我们开发了一种定量活细胞成像方法来分析蛋白质分选和高尔基体后囊泡运输。我们重点关注了两个表现出不同定位的树枝状电压门控钾通道：近端树枝状突起中的Kv2.1和远端树枝状突起中的Kv4.2。我们的研究结果表明，Kv2.1和Kv4.2通道分为两个不同的群体的囊泡在高尔基体。Kv2.1和Kv4.2囊泡的靶向通过不同的机制发生，如它们对特定肽基序、细胞骨架元件和马达蛋白的需求所证明的。通过活细胞和超分辨率成像，我们确定了一种新的贩运机制，重要的Kv2.1通道的本地化。特别是，我们确定了非肌肉肌球蛋白II在Kv2.1贩运的一个重要因素。这些研究结果表明，在高尔基体的离子通道的排序和随后的独特的分子机制的贩运是至关重要的树突内的特定定位。
Background: Voltage-gated K+ (Kv) channels are localized in specific dendritic subcompartments of neurons to regulate dendritic excitability. Results: Dendritic Kv channels are sorted and trafficked in distinct populations of post-Golgi transport vesicles. Conclusion: Sorting of Kv channels and their subsequent trafficking by unique mechanisms are crucial for their specific localizations within dendrites. Significance: Our study reveals the existence of novel subcompartment-specific trafficking pathways for dendritic ion channels.Proper membrane localization of ion channels is essential for the function of neuronal cells. Particularly, the computational ability of dendrites depends on the localization of different ion channels in specific subcompartments. However, the molecular mechanisms that control ion channel localization in distinct dendritic subcompartments are largely unknown. Here, we developed a quantitative live cell imaging method to analyze protein sorting and post-Golgi vesicular trafficking. We focused on two dendritic voltage-gated potassium channels that exhibit distinct localizations: Kv2.1 in proximal dendrites and Kv4.2 in distal dendrites. Our results show that Kv2.1 and Kv4.2 channels are sorted into two distinct populations of vesicles at the Golgi apparatus. The targeting of Kv2.1 and Kv4.2 vesicles occurred by distinct mechanisms as evidenced by their requirement for specific peptide motifs, cytoskeletal elements, and motor proteins. By live cell and super-resolution imaging, we identified a novel trafficking machinery important for the localization of Kv2.1 channels. Particularly, we identified non-muscle myosin II as an important factor in Kv2.1 trafficking. These findings reveal that the sorting of ion channels at the Golgi apparatus and their subsequent trafficking by unique molecular mechanisms are crucial for their specific localizations within dendrites.