Saltatory conduction — the process by which action potentials propagate along myelinated nerves — depends on the fact that voltage-gated Na+ channels form clusters at the nodes of Ranvier, between sections of the myelin sheath. New findings from Eshed et al. show that Schwann cells produce a protein called gliomedin, and that this is responsible for the clustering of these channels.

The formation of the nodes of Ranvier is specified by the myelinating cells, not the axons, and an important component of this process in the peripheral nervous system is the extension of microvilli by Schwann cells. These microvilli contact the axons at the nodes, and it is here that the Schwann cells express the newly discovered protein gliomedin.

Eshed et al. showed that gliomedin is a ligand for two axonal cell adhesion molecules — neurofascin and NrCAM — that are found at the nodes of Ranvier, where they interact with Na+ channels. When the authors either disrupted the localization of gliomedin by using a soluble fusion protein that contained the extracellular domain of neurofascin, or used RNA interference to suppress the expression of gliomedin, the characteristic clustering of Na+ channels at the nodes of Ranvier did not occur.

Aggregation of the domain of gliomedin that binds neurofascin and NrCAM on the surface of purified neurons also caused the clustering of neurofascin, Na+ channels and other nodal proteins. These findings support a model in which gliomedin on Schwann cell microvilli binds to neurofascin and NrCAM on axons, causing them to cluster at the nodes of Ranvier, and leading to the formation of complexes that contain Na+ channels.