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

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

Mesh terms: Animals | Ankyrins | Axons | Base Sequence | Brain | Cells, Cultured | Cytoskeleton | Gene Deletion | Gene Expression Profiling | Hindlimb | Ion Channel Gating | Mice | Mice, Knockout | Mice, Mutant Strains | Molecular Sequence Data | Nerve Tissue Proteins | Phenotype | Protein Isoforms | Protein Transport | RNA, Messenger | Ranvier's Nodes | Retroviridae | Sodium Channels | Spectrin | Tremor

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Associated grants

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

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Mouse Genome Informatics

An international database for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human health and disease. Its primary mission is to facilitate the use of the mouse as a model system for understanding human biology and disease. MGI creates and maintains an integrated representation of mouse genetic, genomic, expression, and phenotype data and develops definitive reference data set and consensus data views. MGI also synthesizes comparative genomic data between the mouse and other mammals, maintains a set of links and collaborations with other bioinformatics resources, develops and supports analysis and data submission tools, and provides extensive technical support for database users. The 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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