Work

βIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier

Year: 2002

Type: article

Abstract: 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.

Source: The Journal of Cell Biology

DOI: 10.1083/jcb.200110003

Authors: Masayuki Komada, Philippe Soriano

Institutions: Tokyo Institute of Technology, Fred Hutch Cancer Center

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: RIKEN, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, RIKEN Brain Science Institute

Award: Gene Expression, Function and Mutagenesis