title: The paranodal cytoskeleton clusters Na+channels at nodes of Ranvier.
abstract: A high density of Na+channels at nodes of Ranvier is necessary for rapid and efficient action potential propagation in myelinated axons. Na+ channel clustering is thought to depend on two axonal cell adhesion molecules that mediate interactions between the axon and myelinating glia at the nodal gap (i.e., NF186) and the paranodal junction (i.e., Caspr). Here we show that while Na+channels cluster at nodes in the absence of NF186, they fail to do so in double conditional knockout mice lacking both NF186 and the paranodal cell adhesion molecule Caspr, demonstrating that a paranodal junction-dependent mechanism can cluster Na+channels at nodes. Furthermore, we show that paranode-dependent clustering of nodal Na+channels requires axonal βII spectrin which is concentrated at paranodes. Our results reveal that the paranodal junction-dependent mechanism of Na+channel clustering is mediated by the spectrin-based paranodal axonal cytoskeleton.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Veronique
authors.initials: V
authors.lastname: Amor
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Vainshtein
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Zollinger
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Eshed-Eisenbach
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brophy
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, United States.
authors.forename: Matthew N
authors.identifier: 0000-0001-8184-2477
authors.initials: MN
authors.lastname: Rasband
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D018345:Mice, Knockout; D011901:Ranvier's Nodes / Q000737:chemistry*; D015222:Sodium Channels / Q000032:analysis*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D015222:Sodium Channels
keywords: axon; ion channel; mouse; myelin; neuroscience