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[Beta]IV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier.

The Journal of cell biology | 2002

beta-Spectrin and ankyrin are major components of the membrane cytoskeleton. We have generated mice carrying a null mutation in the betaIV-spectrin gene using gene trapping in embryonic stem cells. Mice homozygous for the mutation exhibit tremors and contraction of hindlimbs. betaIV-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 betaIV-spectrin-null 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-G-null neurons, betaIV-spectrin is not localized to these sites. These results indicate that betaIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR.

Pubmed ID: 11807096 RIS Download

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Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: R01 HD024875
  • Agency: NICHD NIH HHS, United States
    Id: HD24875

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Mouse Genome Informatics (MGI) (tool)

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International database for laboratory mouse. Data offered by The Jackson Laboratory includes information on integrated genetic, genomic, and biological data. MGI creates and maintains integrated representation of mouse genetic, genomic, expression, and phenotype data and develops reference data set and consensus data views, synthesizes comparative genomic data between mouse and other mammals, maintains set of links and collaborations with other bioinformatics resources, develops and supports analysis and data submission tools, and provides technical support for database users. Projects contributing to this resource are: Mouse Genome Database (MGD) Project, Gene Expression Database (GXD) Project, Mouse Tumor Biology (MTB) Database Project, Gene Ontology (GO) Project at MGI, and MouseCyc Project at MGI.

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COS-7 (tool)

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Cell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)

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