Abstract
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.
Highlights
Voltage-gated Kϩ (Kv) channels are localized in specific dendritic subcompartments of neurons to regulate dendritic excitability
Our results show that Kv2.1 and Kv4.2 channels are sorted into two distinct populations of vesicles at the Golgi apparatus
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
Summary
Voltage-gated Kϩ (Kv) channels are localized in specific dendritic subcompartments of neurons to regulate dendritic excitability. 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. We hypothesized that, within dendrites, multiple biosynthetic trafficking mechanisms exist to target membrane proteins to different and specific subcompartments To test this hypothesis, we focused on Kv2.13 and Kv4.2 channels based on their distinct localizations in dendrites. We uncovered that Kv2.1 and Kv4.2 channels are sorted into different types of transport vesicles, which display different movement dynamics and distribu-
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