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

Tammy Szu Yu Ho, Daniel R. Zollinger, Kae Jiun Chang, Mingxuan Xu, Edward C. Cooper, Michael C. Stankewich, Vann Bennett, Matthew N. Rasband

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


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 bI spectrin substitute for and rescue nodal Na+ channel clustering. In addition, channel clustering is also rescued after loss of nodal bIV spectrin by bI spectrin and ankyrin-R. In mice lacking both ankyrin-G and ankyrin-R, Na+ channels fail to cluster at nodes. Thus, ankyrin R-bI 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.

Original languageEnglish (US)
Pages (from-to)1664-1672
Number of pages9
JournalNature Neuroscience
Issue number12
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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