A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier

Nat Neurosci. 2014 Dec;17(12):1664-72. doi: 10.1038/nn.3859. Epub 2014 Nov 2.


The scaffolding protein ankyrin-G is required for Na(+) channel clustering at axon initial segments. It is also considered essential for Na(+) channel clustering at nodes of Ranvier to facilitate fast and efficient action potential propagation. However, notwithstanding these widely accepted roles, we show here that ankyrin-G is dispensable for nodal Na(+) channel clustering in vivo. Unexpectedly, in the absence of ankyrin-G, erythrocyte ankyrin (ankyrin-R) and its binding partner βI spectrin substitute for and rescue nodal Na(+) channel clustering. In addition, channel clustering is also rescued after loss of nodal βIV spectrin by βI spectrin and ankyrin-R. In mice lacking both ankyrin-G and ankyrin-R, Na(+) channels fail to cluster at nodes. Thus, ankyrin R-βI spectrin protein complexes function as secondary reserve Na(+) channel clustering machinery, and two independent ankyrin-spectrin protein complexes exist in myelinated axons to cluster Na(+) channels at nodes of Ranvier.

Publication types

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

MeSH terms

  • Animals
  • Ankyrins / analysis*
  • Ankyrins / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ranvier's Nodes / chemistry*
  • Ranvier's Nodes / metabolism
  • Rats
  • Sodium Channels / analysis*
  • Sodium Channels / metabolism
  • Spectrin / analysis*
  • Spectrin / metabolism


  • Ankyrins
  • Sodium Channels
  • Spectrin