Nodal β spectrins are required to maintain Na+ channel clustering and axon integrity
Open Access
- 13 February 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
Clustered ion channels at nodes of Ranvier are critical for fast action potential propagation in myelinated axons. Axon-glia interactions converge on ankyrin and spectrin cytoskeletal proteins to cluster nodal Na+ channels during development. However, how nodal ion channel clusters are maintained is poorly understood. Here, we generated mice lacking nodal spectrins in peripheral sensory neurons to uncouple their nodal functions from their axon initial segment functions. We demonstrate a hierarchy of nodal spectrins, where β4 spectrin is the primary spectrin and β1 spectrin can substitute; each is sufficient for proper node organization. Remarkably, mice lacking nodal β spectrins have normal nodal Na+ channel clustering during development, but progressively lose Na+ channels with increasing age. Loss of nodal spectrins is accompanied by an axon injury response and axon deformation. Thus, nodal spectrins are required to maintain nodal Na+ channel clusters and the structural integrity of axons.Funding Information
- National Institutes of Health (NS044916)
- National Institutes of Health (NS069688)
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
This publication has 39 references indexed in Scilit:
- βIV-Spectrin regulates STAT3 targeting to tune cardiac response to pressure overloadJCI Insight, 2018
- Axon initial segments: structure, function, and diseaseAnnals of the New York Academy of Sciences, 2018
- MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent Cargo Transport in Sensory NeuronsNeuron, 2017
- The paranodal cytoskeleton clusters Na+ channels at nodes of RanviereLife, 2017
- Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous systemThe Journal of cell biology, 2008
- βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segmentsThe Journal of cell biology, 2004
- Molecular changes in neurons in multiple sclerosis: Altered axonal expression of Na v 1.2 and Na v 1.6 sodium channels and Na + /Ca 2 + exchangerProceedings of the National Academy of Sciences of the United States of America, 2004
- βiv Spectrin, a New Spectrin Localized at Axon Initial Segments and Nodes of Ranvier in the Central and Peripheral Nervous SystemThe Journal of cell biology, 2000
- Activating Transcription Factor 3 (ATF3) Induction by Axotomy in Sensory and Motoneurons: A Novel Neuronal Marker of Nerve InjuryMolecular and Cellular Neuroscience, 2000
- Dependence of Nodal Sodium Channel Clustering on Paranodal Axoglial Contact in the Developing CNSJournal of Neuroscience, 1999