Hi et al., 2002). Mice lacking raft gangliosides, notably GM1 and GD1a, show alterations in Caspr1/NF155 aggregation at paranodes (Susuki et al., 2007a). In mice lacking Caspr-1 or gangliosides, the partition of NF155 into lipid rafts is strongly attenuated.CONTACTIN-2 AND CASPR-2 AT JUXTAPARANODESThe juxtaparanodal regions are adjacent to the paranodes and are recovered by compact myelin. The juxtaparanodes are enriched in Shaker-type Kv1 channels, mainly Kv1.1, Kv1.2, and Kv1.6 subunits, but additionally Kv1.four inside a subtype of sensory fibers (Rasband et al., 1998; Rasband and Trimmer, 2001). These channels could stabilize conduction by dampening repetitive firing and keeping the internodal resting potential, specifically throughout improvement and in smaller diameter axons (Rasband et al., 1998; Devaux et al., 2002; Devaux and Gow, 2008). A heteromeric complex of Contactin-2 (also called TAG-1) and Caspr-2 is implicated within the formation of juxtaparanodes in both CNS and PNS (Poliak et al., 2003; Traka et al., 2003). These molecules are homologs of Contactin-1 and Caspr-1, respectively. Contactin-2 is expressed at the axonal and glial membranes at juxtaparanodes and displays homophilic binding activity which mediates adhesive get in touch with. Contactin-2 exists as a glycosyl-phosphatidyl-inositol anchored type, as well as a released form (Furley et al., 1990). Inside the axonal membrane, Contactin-2 forms a cis-complex with Caspr-2 by means of its Ig domains which enables the formation of a ternary complicated using the glial-secreted 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 does not 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 gating and motor coordination (Savvaki et al., 2008). Strikingly, the transgenic expression of Contactin-2 exclusively in oligodendrocytes is adequate to rescue juxtaparanode formation along with the behavioral deficits in Contactin-2-deficient mice (Savvaki et al., 2010). These information highlight the significance of glial-secreted Contactin-2. A number of scaffolding proteins (4.1B, ankyrin-B, II- and IIspectrin) are expressed at juxtaparanodes with Caspr-2, but also at paranodes (Denisenko-Nehrbass et al., 2003; Ogawa et al., 2006). In 4.1B-null mice, the accumulation of Caspr-2, Contactin-2, and Kv1.1/Kv1.two at juxtaparanodes is abolished, indicating that 4.1BFrontiers 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.Formula of 1879959-77-9 , 2010; Buttermore et al.1838654-62-8 Data Sheet , 2011; Cifuentes-Diaz et al.PMID:24463635 , 2011a; Einheber et al., 2013). Additionally, the membraneassociated guanylate kinases PSD-93 and PSD-95 are concentrated at juxtaparanodes (Ogawa et al., 2010). Having said that, these proteins aren’t required 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 inside the loss of PSD-93 and -95 at juxtaparanodes, but will not impact the localization of Kv1 channels and Caspr-2. The precise function of disintegrin and ADAM22 at juxtaparanodes, as a result, remai.
