Axon-glia interactions and the domain organization of myelinated axons requires Neurexin IV/Caspr/Paranodin

Myelinated fibers are organized into distinct domains that are necessary fo r saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specia lized septate-like junctions with axons. These junctions contain a Drosophi la Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of N CP1, normal paranodal junctions fail to form, and the organization of the p aranodal loops is disrupted. Contactin is undetectable in the paranodes, an d K+ channels are displaced from the juxtaparanodal into the paranodal doma ins. Loss of NCP1 also results in a severe decrease in peripheral nerve con duction velocity. These results show a critical role for NCP1 in the deline ation of specific axonal domains and the axon-glia interactions required fo r normal saltatory conduction.