Early and late loss of the cytoskeletal scaffolding protein, ankyrin G reveals its role in maturation and maintenance of nodes of Ranvier in myelinated axons

Julia Saifetiarova, Anna M. Taylor, Manzoor A. Bhat

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The mechanisms that govern node of Ranvier organization, stability, and long-term maintenance remain to be fully elucidated. One of the molecular components of the node is the cytoskeletal scaffolding protein, ankyrin G (AnkG), which interacts with multiple members of the nodal complex. The role of AnkG in nodal organization and maintenance is still not clearly defined as to whether AnkG functions as an initial nodal organizer or whether it functions as a nodal stabilizer after the nodal complex has been assembled. Using a mouse model system, we report here that perinatal and juvenile neuronal ablation of AnkG has differential consequences on nodal stability. Early loss of AnkG creates immature nodes with abnormal morphology, which undergo accelerated destabilization within a month, resulting in rapid voltage-gated sodium (NaV) channel and βIV spectrin loss with reduced effects on neurofascin 186. On the other hand, late ablation of AnkG from established nodal complexes leads to slow but progressive nodal destabilization over 10 months, primarily affecting βIV spectrin, followed by NaV channels, with modest impact on neurofascin 186. We also show that ankyrin R and βI spectrin are not sufficient to prevent nodal disorganization after AnkG ablation. Additionally, nodal disorganization in both early and late AnkG mutants is accompanied by axonal pathology and neurological dysfunction. Together, our results suggest that AnkG plays an indispensable role in the maturation and long-term stabilization of the newly assembled nodal complex, and that loss of AnkG after nodal stabilization does not lead to rapid nodal disassembly but to loss of specific nodal components in a time-dependent manner.

Original languageEnglish (US)
Pages (from-to)2524-2538
Number of pages15
JournalJournal of Neuroscience
Volume37
Issue number10
DOIs
StatePublished - Mar 8 2017

Keywords

  • Ankyrin G
  • Axonal domains
  • Myelin
  • Nerve conduction
  • Neurofascin
  • Nodes of ranvier

ASJC Scopus subject areas

  • Neuroscience(all)

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