Three mechanisms assemble central nervous system nodes of ranvier

Keiichiro Susuki, Kae Jiun Chang, Daniel R. Zollinger, Yanhong Liu, Yasuhiro Ogawa, Yael Eshed-Eisenbach, María T. Dours-Zimmermann, Juan A. Oses-Prieto, Alma L. Burlingame, Constanze I. Seidenbecher, Dieter R. Zimmermann, Toshitaka Oohashi, Elior Peles, Matthew N. Rasband

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Abstract

Rapid action potential propagation in myelinated axons requires Na+ channel clustering at nodes of Ranvier. However, the mechanism of clustering at CNS nodes remains poorly understood. Here, we show that the assembly of nodes of Ranvier in the CNS involves three mechanisms: a glia-derived extracellular matrix (ECM) complex containing proteoglycans and adhesion molecules that cluster NF186, paranodal axoglial junctions that function as barriers to restrict the position of nodal proteins, and axonal cytoskeletal scaffolds (CSs) that stabilize nodal Na+ channels. We show that while mice with a single disrupted mechanism had mostly normal nodes, disruptions of the ECM and paranodal barrier, the ECM and CS, or the paranodal barrier and CS all lead to juvenile lethality, profound motor dysfunction, and significantly reduced Na+ channel clustering. Our results demonstrate that ECM, paranodal, and axonal cytoskeletal mechanisms ensure robust CNS nodal Na+ channel clustering

Original languageEnglish
Pages (from-to)469-482
Number of pages14
JournalNeuron
Volume78
Issue number3
DOIs
Publication statusPublished - May 8 2013

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Susuki, K., Chang, K. J., Zollinger, D. R., Liu, Y., Ogawa, Y., Eshed-Eisenbach, Y., Dours-Zimmermann, M. T., Oses-Prieto, J. A., Burlingame, A. L., Seidenbecher, C. I., Zimmermann, D. R., Oohashi, T., Peles, E., & Rasband, M. N. (2013). Three mechanisms assemble central nervous system nodes of ranvier. Neuron, 78(3), 469-482. https://doi.org/10.1016/j.neuron.2013.03.005