Organization and stabilization of the paranodal domain. A: Diagram of the molecular components of the paranode. B,C: Sciatic nerve fibers from wild-type (B) and Caspr−/− (C) mice immuno-stained against potassium channels (KV1.1, red), Caspr (blue), and sodium channels (NaCh, green) reveal the role of the paranodal AGSJs to segregate potassium channels in the JXP from sodium channels in the node (). D,E: Electron micrographs of wild-type (D) and Caspr−/− (E) axons showing parallel arrays of axonal cytoskeleton in the wild-type axon and disorganization of the axonal cytoskel-eton in the Caspr−/− (). F,G: Sciatic nerves from wild-type (F) and Act-Cre;4.1BFlox (G) mice immunostained against Nfasc (a, red), Caspr (b, green), AnkG (c, blue), and merged (d) reveal the disruption of paranodes in P30 4.1B mutant PNS axons. Act-Cre allows ubiquitous expression of Cre under β-actin promoter. H,I: Spinal cord sections from wild-type (H) and Act-Cre;4.1BFlox (I) mice immunostained against 4.1B (a, red), Caspr (b, green), AnkG (c, blue), and merged (d) reveal disruption of the paranode in 4-month-old 4.1B mutant CNS axons. J,M: Electron micrographs of sciatic nerve fibers (J,K) and spinal cord fibers (L,M) from wild-type (J,L) and Act-Cre;4.1BFlox (K,M) mice, revealing disrupted AGSJ compaction in the PNS (K) and loss of AGSJs in the CNS (M; ). Scale bars = 20 µm in C (applies to B,C); 10 µm in F (applies to F,G); 5 µm in H (applies to H,I); 0.2 µm in J–M. (B,C: Reprinted from Neuron 2001; 30:369–383, with permission from Elsevier; D,E: © Garcia-Fresco GP, Sousa AD, Pillai AM, Moy SS, Crawley JN, Tessarollo L, Dupree JL, Bhat MA. Disruption of axo–glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons. Originally published in Proc Natl Acad Sci USA 2006; 103:5137–5142; F–M: Reprinted from J Neurosci 2011; 31:8013–8024, with permission from The Journal of Neuroscience.)