Sodium channel β subunits modulate channel kinetic properties and cell surface expression levels and function as cell adhesion molecules. β1 and β2 participate in homophilic cell adhesion resulting in ankyrin recruitment to cell contact sites. We hypothesized that a tyrosine residue in the cytoplasmic domain of β1 may be important for ankyrin recruitment and tested our hypothesis using β1 mutants replacing Tyr181 with alanine (β1Y181A), phenylalanine (β1Y181F), or glutamate (β1Y181E), or a truncated construct deleting all residues beyond Tyr181(β1L182STOP). Ankyrin recruitment was observed in β1L182STOP, showing that residues Ile166-Tyr181 contain the major ankyrin recruiting activity of β1. Ankyrin recruitment was abolished in β1Y181E, suggesting that tyrosine phosphorylation of β1 may inhibit β1-ankyrin interactions. AnkyrinG and β1 associate in rat brain membranes and in transfected cells expressing β1 and ankyrinG in the absence of sodium channel α subunits. β1 subunits are recognized by anti-phosphotyrosine antibodies following treatment of these cell lines with fibroblast growth factor. β1 and ankryinG association is not detectable in cells following treatment with fibroblast growth factor. AnkyrinG and β1Y181E do not associate even in the absence of fibroblast growth factor treatment. β1 subunit-mediated cell adhesion and ankyrin recruitment may contribute to sodium channel placement at nodes of Ranvier. The phosphorylation state of β1Y181 may be a critical regulatory step in these developmental processes.
Structural Requirements for Interaction of Sodium Channel β1 Subunits with Ankyrin*
J. Malhotra,M. Koopmann,K. Kazen-Gillespie,Nicholas Fettman,M. Hortsch,L. Isom
Published 2002 in Journal of Biological Chemistry
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- Publication year
2002
- Venue
Journal of Biological Chemistry
- Publication date
2002-07-19
- Fields of study
Biology
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