Rapid propagation of action potentials along myelinated axons depends on the high-density accumulation of voltage-gated Na+ channels at regularly spaced interruptions in the myelin known as the nodes of Ranvier. In the PNS, direct contact between the axon and myelinating Schwann cells is necessary for clustering of Na+ channels, although the underlying mechanism is not clear. This lecture will discuss recent studies showing that myelinating Schwann cells control the molecular assembly of nodes by two distinct mechanisms that require different adhesion complexes, each of which mediate distinct axon-glia interactions at the developing nodes and the adjacent paranodes. Together, these cooperating mechanisms ensure that Na+ channels are found at high density at the nodes.

Feinberg et al., (2010) A glial signal consisting of Gliomedin and NrCAM clusters axonal Na+ channel during the formation of nodes of Ranvir. Neuron 65:490-502. Horresh et al (2010) Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adaptor protein 4.1B. J. Neurosci. 30:2480-2489.