Aranodes, and juxtaparanodes. Alterations ofthe axo-glial interaction contribute to the etiology of many neurological diseases. This article evaluations current findings documenting the implication of CAMs in axon specialization and in neurological ailments.MOLECULAR ORGANIZATION On the AXONAL DOMAINS OF MYELINATED FIBERSNEUROFASCIN-186, NrCAM, AND GLIOMEDIN: STRUCTURE AND FUNCTION AT PNS NODESDuring improvement, the clustering of Nav is strongly dependent around the axo-glial contact at PNS nodes of Ranvier (MelendezVasquez et al., 2001), but also on two scaffolding proteins, ankyrinG and IV-spectrin, which links the nodal proteins to the actin cytoskeleton (Jenkins and Bennett, 2002; Komada and Soriano, 2002; Yang et al., 2004; Devaux, 2010). Within the PNS, the myelinating Schwann cells kind the nodal microvilli which face the nodes of Ranvier. Various CAMs expressed at nodal axolemma or secreted by Schwann cells at the nodal lumen mediate the axo-glial contact and the clustering of Nav channels (Nav1.2 and Nav1.6) at nodes of Ranvier (Caldwell et al., 2000; Boiko et al., 2001). Neurofascin-186 (NF186) and NrCAM belong to the L1-family of CAMs and are concentrated at the nodes of Ranvier (Davis et al., 1996). NF186 is expressed at the nodal axolemma only. By contrast, NrCAM IL-6 Inhibitor manufacturer exists as each an axonal form and also a kind secreted by the Schwann cell microvilli (Feinberg et al., 2010). Both NF186 and NrCAM bind Gliomedin, an extracellular matrix component secreted by the Schwann cell microvilli (Figure 1A). Gliomedin consists of a coiled-coil, two collagen-like, and one olfactomedin domain (Eshed et al., 2005). Gliomedin exists as each transmembrane and secreted forms (Eshed et al.,Frontiers in Cellular Caspase 10 Inhibitor Synonyms Neurosciencefrontiersin.orgOctober 2013 | Volume 7 | Report 196 |Faivre-Sarrailh and DevauxNeuro-glial interactions at nodesFIGURE 1 | Organization of CNS and PNS nodes of Ranvier. (A) At PNS nodes, NF186 binds Gliomedin (Gldn) and NrCAM that are secreted by Schwann cells within the nodal gap lumen. The cytoplasmic area of axonal NF186 and NrCAM bind ankyrin-G, which anchors the nodal complex to IV-spectrin and to the actin cytoskeleton. Ankyrin-G enables the clustering of Nav and Kv7 .3 channels at nodes. (B) In the CNS, Tenascin-R (TN-R), .2/7 Brevican (Bcan), Versican (Vcan), and Phosphacan (Phcan) are enriched within the extracellular matrix surrounding the nodes, and stabilize the nodal complex.These molecules bind NF186, NrCAM, and Contactin-1 which are expressed at CNS nodes. (C) The complicated Contactin-1/Caspr-1/NF155 forms the septate-like junctions at each PNS and CNS paranodes. This complex is stabilized by the cytosolic protein 4.1B which co-localizes with ankyrin-B, IIand II-spectrin at both paranodes and juxtaparanodes. (D) The complicated Contactin-2/Caspr-2 enables the sequestration of Kv1.1/Kv1.2/Kv1.six channels at juxtaparanodes, but also of PSD-93 and PSD-95. ADAM22 and Connexin-29 (Cx29) are also enriched at juxtaparanodes.2007; Maertens et al., 2007). However, solely the secreted type, generated by proteolytic cleavage with furin and BMP-1 enzymes, is detected in the nodes of Ranvier. The release from the C-terminal olfactomedin domain favors its oligomerization, its incorporation within the extracellular matrix, and its interaction with NF186. The interactions amongst Gliomedin, NF186, and NrCAM are important for the initial clustering with the Nav channels at hemi-nodes. In the developing sciatic nerve or in myelinating co-cultures of dorsal root gang.
