Mechanisms of node of Ranvier assembly

The nodes of Ranvier have clustered Na + and K + channels necessary for rapid and efficient axonal action potential conduction. However, detailed mechanisms of channel clustering have only recently been identified: they include two independent axon–glia interactions that converge on distinct axonal cytoskeletons. Here, we discuss how glial cell adhesion molecules and the extracellular matrix molecules that bind them assemble combinations of ankyrins, spectrins and other cytoskeletal scaffolding proteins, which cluster ion channels. We present a detailed molecular model, incorporating these overlapping mechanisms, to explain how the nodes of Ranvier are assembled in both the peripheral and central nervous systems. The formation of the nodes of Ranvier in myelinated axons involves a specific clustering of ion channels. In this Review, Rasband and Peles describe two independent, glia-directed mechanisms that converge on the axonal cytoskeleton to cluster and maintain nodal ion channels.