title: Specific role of the truncated betaIV-spectrin Sigma6 in sodium channel clustering at axon initial segments and nodes of ranvier.
abstract: At axon initial segments and nodes of Ranvier in neurons, the spectrin membrane skeleton plays roles in physically stabilizing the plasma membrane integrity and in clustering voltage-gated sodium channels for proper conduction of the action potential. betaIV-Spectrin, an essential component of the membrane skeleton at these sites, has an N-terminal-truncated isoform, Sigma6, which is expressed at much higher levels than the full-length isoform Sigma1. To investigate the role of betaIV-spectrin Sigma6, we generated Sigma1-deficient mice with a normal level of Sigma6 expression (Sigma1(-/-) mice), and compared their phenotypes with those of previously generated mice lacking both Sigma1 and Sigma6(Sigma1Sigma6(-/-) mice). The gross neurological defects observed in Sigma1Sigma6(-/-) mice, such as hindleg contraction, were apparently ameliorated in Sigma1(-/-) mice. At cellular levels, Sigma1Sigma6(-/-) and Sigma1(-/-) neurons similarly exhibited waving and swelling of the plasma membrane at axon initial segments and nodes of Ranvier. By contrast, the levels of ankyrin G and voltage-gated sodium channels at these sites, which are significantly reduced in Sigma1Sigma6(-/-) mice, were substantially recovered in Sigma1(-/-) mice. We conclude that the truncated betaIV-spectrin isoform Sigma6 plays a specific role in clustering voltage-gated sodium channels, whereas it is dispensable for membrane stabilization at axon initial segments and nodes of Ranvier.
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Uemoto
authors.forename: So-Ichiro
authors.initials: S
authors.lastname: Suzuki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Terada
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ohno
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohno
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komada
mesh_terms: D000818:Animals; D001369:Axons / Q000737:chemistry*; D003599:Cytoskeleton; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009474:Neurons; D010641:Phenotype; D020033:Protein Isoforms; D011901:Ranvier's Nodes / Q000737:chemistry*; D015222:Sodium Channels / Q000378:metabolism*; D013049:Spectrin / Q000032:analysis / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D015222:Sodium Channels; C504042:betaIV spectrin, mouse; D013049:Spectrin