Mechanisms of node of Ranvier assembly

Nat Rev Neurosci. 2021 Jan;22(1):7-20. doi: 10.1038/s41583-020-00406-8. Epub 2020 Nov 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ankyrins / metabolism
  • Axons / metabolism
  • Cell Adhesion Molecules / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Ion Channels / metabolism
  • Neuroglia / metabolism*
  • Neurons / metabolism*
  • Ranvier's Nodes / metabolism*
  • Spectrin / metabolism


  • Ankyrins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Ion Channels
  • Spectrin