Published 21 January 2002. doi:10.1083/jcb.200110003
© The Rockefeller University Press,
0021-9525/2002/1/337 $5.00
The Journal of Cell Biology, Volume 156, Number 2, January 21, 2002 337-348
ßIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier
Masayuki Komada1,2 and
Philippe Soriano1
1 Program in Developmental Biology and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
2 Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
Address correspondence to Masayuki Komada, Dept. of Life Sciences, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan. Tel.: 81-45-924-5702. Fax: 81-45-924-5771. E-mail: makomada{at}bio.titech.ac.jp
ß-Spectrin and ankyrin are major components of the membrane cytoskeleton. We have generated mice carrying a null mutation in the ßIV-spectrin gene using gene trapping in embryonic stem cells. Mice homozygous for the mutation exhibit tremors and contraction of hindlimbs. ßIV-spectrin expression is mostly restricted to neurons, where it colocalizes with and binds to ankyrin-G at axon initial segments (AISs) and nodes of Ranvier (NR). In ßIV-spectrinnull neurons, neither ankyrin-G nor voltage-gated sodium channels (VGSC) are correctly clustered at these sites, suggesting that impaired action potential caused by mislocalization of VGSC leads to the phenotype. Conversely, in ankyrin-Gnull neurons, ßIV-spectrin is not localized to these sites. These results indicate that ßIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR.
Key Words: ßIV-spectrin; ankyrin-G; voltage-gated sodium channel; axon initial segment; node of Ranvier

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