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The Microtubule Plus-End Tracking Protein EB1 Is Required for Kv1 Voltage-Gated K+ Channel Axonal Targeting

by: Chen Gu, Wei Zhou, Manojkumar A Puthenveedu, Mingxuan Xu, Yuh N Jan, Lily Y Jan
Neuron, Vol. 52, No. 5. (7 December 2006), pp. 803-816.


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SummaryAxonal Kv1 channels regulate action potential propagation--an evolutionarily conserved function important for the control of motor behavior as evidenced from the linkage of human Kv1 channel mutations to myokymia/episodic ataxia type 1 (EA1) and the Shaker mutant phenotype in Drosophila. To search for the machinery that mediates axonal targeting of Kv1 channels composed of both [alpha] and [beta] subunits, we first demonstrate that Kv[beta]2 is responsible for targeting Kv1 channels to the axon. Next, we show that Kv[beta]2 axonal targeting depends on its ability to associate with the microtubule (MT) plus-end tracking protein (+TIP) EB1. Not only do Kv[beta]2 and EB1 move in unison down the axon, Brefeldin A-sensitive Kv1-containing vesicles can also be found at microtubule ends near the cell membrane. In addition, we found that Kv[beta]2 associates with KIF3/kinesin II as well. Indeed, Kv1 channels rely on both KIF3/kinesin II and EB1 for their axonal targeting.


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