Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels

Rapid conduction in myelinated axons depends on the generation of specializ ed subcellular domains to which different sets of ion channels are localize d. Here, we describe the identification of Caspr2, a mammalian homolog of D rosophila Neurexin IV (Nrx-IV), and show that this neurexin-like protein an d the closely related molecule Caspr/Paranodin demarcate distinct subdomain s in myelinated axons. While contactin-associated protein (Caspr) is presen t at the paranodal junctions, Caspr2 is precisely colocalized with Shaker-l ike K+ channels in the juxtaparanodal region. We further show that Caspr2 s pecifically associates with Kv1.1, Kv1.2, and their Kv beta 2 subunit. This association involves the C-terminal sequence of Caspr2, which contains a p utative PDZ binding site. These results suggest a role for Caspr family mem bers in the local differentiation of the axon into distinct functional subd omains.