title: Submembranous cytoskeletons stabilize nodes of Ranvier.
abstract: 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.
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, OH, United States. Electronic address: keiichiro.susuki@wright.edu.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Susuki
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, OH, United States.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otani
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States. Electronic address: rasband@bcm.edu.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Rasband
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D011901:Ranvier's Nodes / Q000502:physiology*; D013049:Spectrin / Q000378:metabolism
chemical_list: D017487:Ankyrins; D007473:Ion Channels; D013049:Spectrin
keywords: Ankyrin; Node of Ranvier; Paranode; Protein 4.1; Spectrin