Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Axons / metabolism*
-
Axons / ultrastructure*
-
Blotting, Northern
-
Fluorescent Antibody Technique, Indirect
-
Humans
-
Immunohistochemistry
-
Kv1.1 Potassium Channel
-
Membrane Proteins / biosynthesis
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Mice
-
Microscopy, Electron
-
Molecular Sequence Data
-
Nerve Fibers, Myelinated / metabolism*
-
Nerve Fibers, Myelinated / ultrastructure*
-
Nerve Tissue Proteins / biosynthesis
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / metabolism*
-
Nervous System / metabolism
-
Potassium Channels / metabolism*
-
Potassium Channels, Voltage-Gated*
-
Precipitin Tests
-
Rats
Substances
-
CNTNAP2 protein, human
-
CNTNAP2 protein, mouse
-
KCNA1 protein, human
-
Kcna1 protein, mouse
-
Membrane Proteins
-
Nerve Tissue Proteins
-
Potassium Channels
-
Potassium Channels, Voltage-Gated
-
Kv1.1 Potassium Channel