[New insights on the organization of the nodes of Ranvier]

Myelin plays a crucial role in the rapid and saltatory conduction of the nerve impulse along myelinated axons. In addition, myelin closely regulates the organization of the axonal compartments. This organization involves several complex mechanisms including axo-glial contact, diffusion barriers, the cytoskeletal network, and the extracellular matrix. In peripheral nerves, the axo-glial contact dictates the formation of the nodes and the clustering of the voltage-gated sodium channels (Nav). The axo-glial contact at nodes implicates adhesion molecules expressed by the Schwann cell (gliomedin and NrCAM), which binds a partner, neurofascin-186, on the axonal side. This complex is essential for the recruitment of ankyrin-G, a cytoskeletal scaffolding protein, which binds and concentrates Nav channels at nodes. The paranodal junctions flanking the nodes also play a complementary function in node formation. These junctions are formed by the association of contactin-1/caspr-1/neurofascin-155 and create a diffusion barrier, which traps proteins at the nodes and dampens their diffusion along the internode. In the central nervous system, the mechanisms of node formation are different and the formation of the paranodal junctions precedes the aggregation of Nav channels at nodes. However, node formation can still happen in absence of paranodal junctions in the CNS. One explanation is that NF186 interacts with components of the extracellular matrix around the node and thereby stabilizes the aggregation of nodal proteins. It is likely that many other proteins are also implicated in the signaling pathways that regulate the differentiation of the axonal compartments. The nature and function of these proteins are yet to be identified.