Juxtaparanodal clustering of Shaker-like K⁺ channels in myelinated axons depends on Caspr2 and TAG-1

In myelinated axons, K⁺ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily. Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K⁺ channels at this location. Furthermore, we show that the localization of Caspr2 and clustering of K⁺ channels at the juxtaparanodal region depends on the presence of TAG-1, an immunoglobulin-like cell adhesion molecule that binds Caspr2. These results demonstrate that Caspr2 and TAG-1 form a scaffold that is necessary to maintain K⁺ channels at the juxtaparanodal region, suggesting that axon–glia interactions mediated by these proteins allow myelinating glial cells to organize ion channels in the underlying axonal membrane.