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.
Poliak
S
S
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Gollan
L
L
Martinez
R
R
Custer
A
A
Einheber
S
S
Salzer
J L
JL
Trimmer
J S
JS
Shrager
P
P
Peles
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure*; D015152:Blotting, Northern; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D051662:Kv1.1 Potassium Channel; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests; D051381:Rats
C403049:CNTNAP2 protein, human; C568163:CNTNAP2 protein, mouse; C496946:KCNA1 protein, human; C496947:Kcna1 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel