Figure 1. Caspr and Caspr2, respectively, dictate the location and membrane accumulation of Kv1 channels at the nodal environ. A, Caspr and Caspr2 are not detectable in dKO mice. Immunofluorescence of teased sciatic nerves isolated from WT, Caspr-null (Caspr−/−), Caspr2-null (Caspr2−/−), and dKO mice using antibodies to Caspr, Caspr2, and Na+ channels (NaCh). The location of the nodes and the juxtaparanodal region are labeled with asterisks and arrowheads, respectively. Note that Caspr2 is mislocalized at the paranodes in the absence of Caspr, whereas the distribution of Caspr is unchanged in the absence of Caspr2. B, C, Absence of both Caspr and Caspr2 does not lead to myelin abnormalities. Immunofluorescence analysis using antibodies to P0, neurofilament (NF) and NaCh (B), as well as electron microscopy analysis of cross-sections (C) of sciatic nerves isolated from the indicated genotypes. D, E, Absence of Caspr or Caspr2 results in altered distribution of juxtaparanodal components. Shown is immunofluorescence labeling of teased sciatic nerves isolated from the indicated genotypes using antibodies to NaCh and Kv1.2 potassium channels (D) or CNTN2 (E). The location of the nodes of Ranvier is marked with an asterisk in all panels. In the absence of Caspr2, Kv1.2 channels are not accumulated at the juxtaparanodal region, but are occasionally detected at the double mesaxonal lines that passed through this region (arrow). Arrowhead marks the presence of abnormal patches of Kv1 channels at the edge of the juxtaparanodal region in the dKO nerves. Scale bars: A, B, D, E, 10 μm; C, 5 μm.