Abstract
Specific cell adhesion molecules (CAMs) are dedicated to the formation of axo-glial contacts at the nodes of Ranvier of myelinated axons. They play a central role in the organization and maintenance of the axonal domains: the node, paranode, and juxtaparanode. In particular, CAMs are essential for the accumulation of voltage-gated sodium channels at the nodal gap that ensures the rapid and saltatory propagation of the action potentials (APs). The mechanisms regulating node formation are distinct in the central and peripheral nervous systems, and recent studies have highlighted the relative contribution of paranodal junctions and nodal extracellular matrix. In addition, CAMs at the juxtaparanodal domains mediate the clustering of voltage-gated potassium channels which regulate the axonal excitability. In several human pathologies, the axo-glial contacts are altered leading to disruption of the nodes of Ranvier or mis-localization of the ion channels along the axons. Node alterations and the failure of APs to propagate correctly from nodes to nodes along the axons both contribute to the disabilities in demyelinating diseases. This article reviews the mechanisms regulating the association of the axo-glial complexes and the role of CAMs in inherited and acquired neurological diseases.
Highlights
In vertebrate, most axons are insulated by myelin sheaths and the action potentials (APs) are regenerated at the nodes of Ranvier which enable the rapid saltatory propagation of the nerve impulses
The myelin is formed by glial cells: Schwann cells in peripheral nervous system (PNS) and oligodendrocytes in central nervous system (CNS)
NEUROFASCIN-186, NrCAM, AND GLIOMEDIN: STRUCTURE AND FUNCTION AT PNS NODES During development, the clustering of Nav is strongly dependent on the axo-glial contact at PNS nodes of Ranvier (MelendezVasquez et al, 2001), and on two scaffolding proteins, ankyrinG and βIV-spectrin, which links the nodal proteins to the actin cytoskeleton (Jenkins and Bennett, 2002; Komada and Soriano, 2002; Yang et al, 2004; Devaux, 2010)
Summary
Most axons are insulated by myelin sheaths and the action potentials (APs) are regenerated at the nodes of Ranvier which enable the rapid saltatory propagation of the nerve impulses. The voltage-gated Na+ (Nav) channels are aggregated at hemi-nodes which border the myelinated segments (Vabnick et al, 1996) These hemi-nodes fuse into a node of Ranvier as the myelin segments grow and approach each over (See Figure 2). Electron microscopic observations revealed that the paranodal loops form septate-like junctions with the axon (Einheber et al, 1997) These junctions may preclude current leakage across the paranodes and favor rapid propagation. Recent evidences indicate that the association of Contactin-1/Caspr-1/Neurofascin-155 (NF155) is required for the formation of the septate-like junctions These junctions favor the sequestration of the voltage-gated potassium channels (VGKCs; Kv), Kv1.1/Kv1.2/Kv1.6, in the juxtaparanodal regions (Vabnick et al, 1999). This article reviews recent findings documenting the implication of CAMs in axon specialization and in neurological diseases
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