Specific Sorting and Post-Golgi Trafficking of Dendritic Potassium Channels in Living Neurons

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.