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Mechanisms of node of Ranvier assembly

Abstract

The nodes of Ranvier have clustered Na+ and K+ channels necessary for rapid and efficient axonal action potential conduction. However, detailed mechanisms of channel clustering have only recently been identified: they include two independent axon–glia interactions that converge on distinct axonal cytoskeletons. Here, we discuss how glial cell adhesion molecules and the extracellular matrix molecules that bind them assemble combinations of ankyrins, spectrins and other cytoskeletal scaffolding proteins, which cluster ion channels. We present a detailed molecular model, incorporating these overlapping mechanisms, to explain how the nodes of Ranvier are assembled in both the peripheral and central nervous systems.

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Fig. 1: Organization of the nodal environ.
Fig. 2: Two overlapping axoglial adhesion systems assemble the nodes of Ranvier.
Fig. 3: Molecular interactions at the nodes of Ranvier.
Fig. 4: A model for glia-directed placement of axonal cytoskeletal scaffolds and barriers.

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Acknowledgements

This work was supported by NIH grants NS044916 (MNR), NS069688 (MNR) and NS097428 (EP), the United States–Israel Binational Science Foundation, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. We thank Drs Yael Eshed-Eisenbach and Kae-jiun Chang for insightful comments on the manuscript. We acknowledge the contributions of our colleagues whose work was not referenced here due to space limitations.

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Correspondence to Matthew N. Rasband or Elior Peles.

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Glossary

Axolemma

The plasma membrane of the axon.

Extracellular matrix

(ECM). A complex mixture of extracellular macromolecules, including glycoproteins, that surround cells.

Microvilli

Small membrane protrusions that increase the surface area of a cell to facilitate adhesion, absorption, or signal transduction.

Splice variant

variants of a gene product that are produced by alternative splicing of the RNA.

Heminodes

The ends of a myelin segment lacking another flanking myelin segment.

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Rasband, M.N., Peles, E. Mechanisms of node of Ranvier assembly. Nat Rev Neurosci 22, 7–20 (2021). https://doi.org/10.1038/s41583-020-00406-8

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