Familial epilepsies are often caused by mutations of voltage-gated Na <sup>+</sup> channels, but correlation genotype-phenotype is not yet clear. In particular, the cause of phenotypic variability observed in some epileptic families is unclear. We studied Na<sub>v</sub>1.1 (SCN1A) Na<sup>+</sup> channel α subunit M1841T mutation, identified in a family characterized by a particularly large phenotypic spectrum. The mutant is a loss of function becausewhenexpressed alone, the current was no greater than background. Function was restored by incubation at temperature &lt;30°C, showing that the mutant is trafficking defective, thus far the first case among neuronal Na<sup>+</sup> channels. Importantly, also molecular interactions with modulatory proteins or drugs were able to rescue the mutant. Protein-protein interactions may modulate the effect of the mutation in vivo and thus phenotype; variability in their strength may be one of the causes of phenotypic variability in familial epilepsy. Interacting drugs may be used to rescue the mutant in vivo. Copyright © 2007 Society for Neuroscience.

Rusconi, R., Scalmani, P., Restano Cassulini, R., Giunti, G., Gambardella, A., Franceschetti, S., et al. (2007). Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 (SCN1A) Na+ channel mutant. THE JOURNAL OF NEUROSCIENCE, 27(41), 11037-11046 [10.1523/JNEUROSCI.3515-07.2007].

Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 (SCN1A) Na+ channel mutant

WANKE, ENZO;
2007

Abstract

Familial epilepsies are often caused by mutations of voltage-gated Na + channels, but correlation genotype-phenotype is not yet clear. In particular, the cause of phenotypic variability observed in some epileptic families is unclear. We studied Nav1.1 (SCN1A) Na+ channel α subunit M1841T mutation, identified in a family characterized by a particularly large phenotypic spectrum. The mutant is a loss of function becausewhenexpressed alone, the current was no greater than background. Function was restored by incubation at temperature <30°C, showing that the mutant is trafficking defective, thus far the first case among neuronal Na+ channels. Importantly, also molecular interactions with modulatory proteins or drugs were able to rescue the mutant. Protein-protein interactions may modulate the effect of the mutation in vivo and thus phenotype; variability in their strength may be one of the causes of phenotypic variability in familial epilepsy. Interacting drugs may be used to rescue the mutant in vivo. Copyright © 2007 Society for Neuroscience.
Articolo in rivista - Articolo scientifico
ion channel mutation, epilepsy
English
11037
11046
Rusconi, R., Scalmani, P., Restano Cassulini, R., Giunti, G., Gambardella, A., Franceschetti, S., et al. (2007). Modulatory proteins can rescue a trafficking defective epileptogenic Nav1.1 (SCN1A) Na+ channel mutant. THE JOURNAL OF NEUROSCIENCE, 27(41), 11037-11046 [10.1523/JNEUROSCI.3515-07.2007].
Rusconi, R; Scalmani, P; Restano Cassulini, R; Giunti, G; Gambardella, A; Franceschetti, S; Annesi, G; Wanke, E; Mantegazza, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/8059
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