Article | Published:

Glial ankyrins facilitate paranodal axoglial junction assembly

Nature Neuroscience volume 17, pages 16731681 (2014) | Download Citation

Abstract

Neuron-glia interactions establish functional membrane domains along myelinated axons. These include nodes of Ranvier, paranodal axoglial junctions and juxtaparanodes. Paranodal junctions are the largest vertebrate junctional adhesion complex, and they are essential for rapid saltatory conduction and contribute to assembly and maintenance of nodes. However, the molecular mechanisms underlying paranodal junction assembly are poorly understood. Ankyrins are cytoskeletal scaffolds traditionally associated with Na+ channel clustering in neurons and are important for membrane domain establishment and maintenance in many cell types. Here we show that ankyrin-B, expressed by Schwann cells, and ankyrin-G, expressed by oligodendrocytes, are highly enriched at the glial side of paranodal junctions where they interact with the essential glial junctional component neurofascin 155. Conditional knockout of ankyrins in oligodendrocytes disrupts paranodal junction assembly and delays nerve conduction during early development in mice. Thus, glial ankyrins function as major scaffolds that facilitate early and efficient paranodal junction assembly in the developing CNS.

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Acknowledgements

E. Peles (Weizmann Institute of Science) provided NfascF/F mice and 4.1G antibodies. K.-A. Nave (Max Planck Institute of Experimental Medicine) provided Cnp-Cre mice. P.M. Jenkins (Duke University) provided AnkG 480/270 antibodies. This work was supported by grants from the US National Institutes of Health (NS069688 and NS044916 to M.N.R.; HL084583, HL083422 and HL114383 to P.J.M.), the National Multiple Sclerosis Society (M.N.R.) and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (M.N.R.). V.B. is an investigator of the Howard Hughes Medical Institute.

Author information

Author notes

    • Keiichiro Susuki

    Present address: Department of Neuroscience, Cell Biology and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA.

Affiliations

  1. Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.

    • Kae-Jiun Chang
    •  & Matthew N Rasband
  2. Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.

    • Daniel R Zollinger
    • , Keiichiro Susuki
    • , Edward C Cooper
    •  & Matthew N Rasband
  3. Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK.

    • Diane L Sherman
    •  & Peter J Brophy
  4. Departments of Physiology and Cell Biology, Internal Medicine, and the Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

    • Michael A Makara
    •  & Peter J Mohler
  5. Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.

    • Edward C Cooper
  6. Department of Cell Biology, Duke University, Durham, North Carolina, USA.

    • Vann Bennett

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Contributions

M.N.R. and K.-J.C. conceived the project, designed the experiments and wrote the manuscript. D.R.Z. and K.S. did electrophysiology experiments and analyzed the data. D.R.Z. conducted the electron microscopy experiments. K.-J.C. did all other experiments and analyzed the data. P.J.M. and M.A.M. designed and constructed the Ank2F/F allele. D.L.S., P.J.B., E.C.C. and V.B. provided reagents and mice.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Matthew N Rasband.

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https://doi.org/10.1038/nn.3858

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