Journal
EXPERIMENTAL NEUROLOGY
Volume 283, Issue -, Pages 446-451Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2015.11.012
Keywords
Node of Ranvier; Paranode; Spectrin; Ankyrin; Protein 4.1
Categories
Funding
- National Multiple Sclerosis Society
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Rapid action potential propagation along myelinated axons requires voltage-gated Na+ (Nav) channel clustering at nodes of Ranvier. At paranodes flanking nodes, myelinating glial cells interact with axons to form junctions. The regions next to the paranodes called juxtaparanodes are characterized by high concentrations of voltage gated K+ channels. Paranodal axoglial junctions function as barriers to restrict the position of these ion channels. These specialized domains along the myelinated nerve fiber are formed by multiple molecular mechanisms including interactions between extracellular matrix, cell adhesion molecules, and cytoskeletal scaffolds. This review highlights recent findings into the roles of submembranous cytoskeletal proteins in the stabilization of molecular complexes at and near nodes. Axonal ankyrin-spectrin complexes stabilize Nav channels at nodes. Axonal protein 4.1B-spectrin complexes contribute to paranode and juxtaparanode organization. Glial ankyrins enriched at paranodes facilitate node formation. Finally, disruption of spectrins or ankyrins by genetic mutations or proteolysis is involved in the pathophysiology of various neurological or psychiatric disorders. (C) 2016 Elsevier Inc. All rights reserved.
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