76 — The Axonal Cytoskeleton and the Assembly of Nodes of Ranvier

Nodes of Ranvier form between myelinated segments of neurites, where high concentrations of voltage-gated sodium channels help amplify the transmission of action-potential across the length of an axon. The mechanism for the assembly of these nodes is still under scrutiny: A better understanding of how these complexes are formed might help inform therapies or treatments for diseases of demyelination. ` First this paper reviews the developmental requisites for healthy node construction. Neurofascin proteins and paranodal axoglial junctions cooperatively attract sodium channels to the nodal vicinity: Each can summon the Nav independently, but healthy axons enlist the help of both in a redundant capacity. If Navs are not concentrated near the nodes when myelination occurs during early development, it results in a fatal condition where the axon fails to conduct action-potentials.

When axoglial contact is made between the prepared axon and an extended process of an oligodendrocyte, the glial processes spread across the surface of the axon until they meet each other. Recently, it came to light that axonal cytoskeleton assists in guiding this process by presenting $\alpha$ and $\beta$ $II$ spectrin along its paranodal regions: $\beta II$ spectrin in particular is important in guiding the distribution of juxtaparanodal proteins, including K channels.

The paper extends a bit further into protein-name soup, but the gist is that we can better understand the nature of demyelination disease, and perhaps even start to point toward therapies, by understanding what causes the myelination in a healthy developmental individual in the first place.