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 specialized subcellular domains to which different sets of ion channels are localized. Here, we describe the identification of Caspr2, a mammalian homolog of Drosophila Neurexin IV (Nrx-IV), and show that this neurexin-like protein and the closely related molecule Caspr/Paranodin demarcate distinct subdomains in myelinated axons. While contactin-associated protein (Caspr) is present at the paranodal junctions, Caspr2 is precisely colocalized with Shaker-like K+ channels in the juxtaparanodal region. We further show that Caspr2 specifically associates with Kv1.1, Kv1.2, and their Kvbeta2 subunit. This association involves the C-terminal sequence of Caspr2, which contains a putative PDZ binding site. These results suggest a role for Caspr family members in the local differentiation of the axon into distinct functional subdomains.
Pubmed ID: 10624965 RIS Download
Amino Acid Sequence | Animals | Axons | Blotting, Northern | Fluorescent Antibody Technique, Indirect | Humans | Immunohistochemistry | Kv1.1 Potassium Channel | Membrane Proteins | Mice | Microscopy, Electron | Molecular Sequence Data | Nerve Fibers, Myelinated | Nerve Tissue Proteins | Nervous System | Potassium Channels | Potassium Channels, Voltage-Gated | Precipitin Tests | Rats