Orms a cis-complex with Caspr-2 by way of its Ig domains which permits the formation of a ternary complex with the glial-secreted L-type calcium channel Inhibitor drug Contactin-2 (Savvaki et al., 2010). Disruption of Caspr-2 or Contactin-2 in knock-out mice prevents the accumulation of Kv1 channels at juxtaparanodes and induces their diffusion along the internodes. Albeit, the mis-localization of Kv1 channels doesn’t influence nerve conduction (Poliak et al., 2003; Traka et al., 2003), it was reported that Contactin-2-deficient animals show behavioral deficits and defects in sensori-motor Caspase Activator supplier gating and motor coordination (Savvaki et al., 2008). Strikingly, the transgenic expression of Contactin-2 exclusively in oligodendrocytes is adequate to rescue juxtaparanode formation plus the behavioral deficits in Contactin-2-deficient mice (Savvaki et al., 2010). These data highlight the value of glial-secreted Contactin-2. Numerous scaffolding proteins (four.1B, ankyrin-B, II- and IIspectrin) are expressed at juxtaparanodes with Caspr-2, but in addition at paranodes (Denisenko-Nehrbass et al., 2003; Ogawa et al., 2006). In four.1B-null mice, the accumulation of Caspr-2, Contactin-2, and Kv1.1/Kv1.2 at juxtaparanodes is abolished, indicating that four.1BFrontiers in Cellular Neurosciencefrontiersin.orgOctober 2013 | Volume 7 | Post 196 |Faivre-Sarrailh and DevauxNeuro-glial interactions at nodesprotein is crucial for the formation of juxtaparanodal domains (Horresh et al., 2010; Buttermore et al., 2011; Cifuentes-Diaz et al., 2011a; Einheber et al., 2013). Additionally, the membraneassociated guanylate kinases PSD-93 and PSD-95 are concentrated at juxtaparanodes (Ogawa et al., 2010). Nonetheless, these proteins aren’t necessary for Kv1 and Caspr-2 clustering at juxtaparanodes (Horresh et al., 2010; Ogawa et al., 2010). The juxtaparanodal complicated also comprises disintegrin and metalloproteinase 22 (ADAM22). The deletion of ADAM22 results in the loss of PSD-93 and -95 at juxtaparanodes, but does not impact the localization of Kv1 channels and Caspr-2. The precise function of disintegrin and ADAM22 at juxtaparanodes, as a result, remains to be determined. Of interest, the loss in the paranodal septate-like junctions in Caspr-1 and Contactin-1 deficient mice induces the re-location of the juxtaparanodal proteins near the nodes (Bhat et al., 2001; Boyle et al., 2001). The function of four.1B in paranode formation or maintenance is uncertain. Nonetheless, the transgenic expression of Caspr-1 lacking the 4.1-binding module in Caspr-null mice restores paranode formation, but will not restore the accumulation of Kv1 channels at juxtaparanodes (Horresh et al., 2010). Altogether, these studies indicate that the organization and upkeep of juxtaparanodes depend on the mixture of 3 distinct processes: assembly of an axo-glial complex at juxtaparanodes, the linkage of this complex for the cytoskeleton, plus the sequestration of this complex by the paranodal diffusion barrier.IMPLICATIONS OF CAMs IN INHERITED AND ACQUIRED NEUROLOGICAL DISORDERSNODE ALTERATIONS IN INHERITED DEMYELINATING DISORDERSAlthough nodal/paranodal CAMs are usually not the priming factors in human inherited demyelinating pathologies, it has came to light through the last decade that demyelination not solely impacts the biophysical properties on the myelinated axons but additionally results inside the redistribution or disorganization from the nodal and paranodal components. These latter alterations likely participate towards the conduction deficits and give important clues about the.
