1. The juvenile myoclonic epilepsy mutant of the calcium channel β4subunit displays normal nuclear targeting in nerve and muscle cells
- Author
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Etemad, Solmaz, Campiglio, Marta, Obermair, Gerald J, and Flucher, Bernhard E
- Abstract
Voltage-gated calcium channels regulate gene expression by controlling calcium entry through the plasma membrane and by direct interactions of channel fragments and auxiliary β subunits with promoters and the epigenetic machinery in the nucleus. Mutations of the calcium channel β4subunit gene (CACNB4) cause juvenile myoclonic epilepsy in humans and ataxia and epileptic seizures in mice. Recently a model has been proposed according to which failed nuclear translocation of the truncated β4subunit R482X mutation resulted in altered transcriptional regulation and consequently in neurological disease. Here we examined the nuclear targeting properties of the truncated β4b(1–481)subunit in tsA-201 cells, skeletal myotubes, and in hippocampal neurons. Contrary to expectation, nuclear targeting of β4b(1–481)was not reduced compared with full-length β4bin any one of the three cell systems. These findings oppose an essential role of the β4distal C-terminus in nuclear targeting and challenge the idea that the nuclear function of calcium channel β4subunits is critically involved in the etiology of epilepsy and ataxia in patients and mouse models with mutations in the CACNB4gene.
- Published
- 2014
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