title: Three mechanisms assemble central nervous system nodes of Ranvier.
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.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Susuki
authors.forename: Kae-Jiun
authors.initials: KJ
authors.lastname: Chang
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Zollinger
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yael
authors.initials: Y
authors.lastname: Eshed-Eisenbach
authors.forename: María T
authors.initials: MT
authors.lastname: Dours-Zimmermann
authors.forename: Juan A
authors.initials: JA
authors.lastname: Oses-Prieto
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.forename: Constanze I
authors.initials: CI
authors.lastname: Seidenbecher
authors.forename: Dieter R
authors.initials: DR
authors.lastname: Zimmermann
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Oohashi
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Rasband
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002490:Central Nervous System / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D011901:Ranvier's Nodes / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D011509:Proteoglycans; D015222:Sodium Channels