Voltage-gated sodium channels in brain neurons were found to associate with receptor protein tyrosine phosphatase β (RPTPβ) and its catalytically inactive, secreted isoform phosphacan, and this interaction was regulated during development. Both the extracellular domain and the intracellular catalytic domain of RPTPβ interacted with sodium channels. Sodium channels were tyrosine phosphorylated and were modulated by the associated catalytic domains of RPTPβ. Dephosphorylation slowed sodium channel inactivation, positively shifted its voltage dependence, and increased whole-cell sodium current. Our results define a sodium channel signaling complex containing RPTPβ, which acts to regulate sodium channel modulation by tyrosine phosphorylation.
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We thank Carl Baker for technical assistance. CFR was supported by a fellowship from the Wellcome Trust. This research was supported by NIH Research Grants NS25704 (W.A.C.) and GM18848 (J.E.D.).
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