Figure 4.

Mechanisms targeting Kv1 channels to the axon. Kvβ2 mediates the axonal targeting of Kv1.2 and Kv1.2-containing heteromers by acting as a cargo adaptor, or a binding partner for an undetermined cargo adaptator for Kif3. Kif3 preferentially transports the Kv1.2/Kvβ2-containing complexes to the axon by a mechanism that requires EB1 in a yet unclear manner. At the level of the AIS, EB1 and EB3 form a complex that interacts with both microtubules and AnkG and possibly acts as a stop signal for the Kv1.2/Kvβ2-containing vesicles. CK2 then leads to release of the vesicle from the microtubules by phosphorylating Kvβ2 which causes its unbinding from EB1. How do the Kv1-containing vesicles recognize their destination site in distal axons and in nodal regions is not known. In addition, the mechanisms by which Kv1 channels get restricted to the juxta-paranodes (JXPN) remains elusive except for an important role of myelin and glial cells. In parallel Kif5B has also been implicated in transporting Kv1.1, Kv1.2 and Kv1.4 to the axon in a mechanism involving the T1 domain, possibly reflecting a similar cargo adaptor role of Kvβ2 interacting with Kv1.2 in this process.