Referenced in: none

Automatically associated channels: Nav1.6 , SK3

Title: The Fibroblast Growth Factor 14{middle dot}Voltage-gated Sodium Channel Complex Is a New Target of Glycogen Synthase Kinase 3 (GSK3).

Authors: Alexander S Shavkunov, Norelle C Wildburger, Miroslav N Nenov, Thomas F James, Tetyana P Buzhdygan, Neli I Panova-Elektronova, Thomas A Green, Ronald L Veselenak, Nigel Bourne, Fernanda Laezza

Journal, date & volume: J. Biol. Chem., 2013 Jul 5 , 288, 19370-85

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23640885

Abstract
The FGF14 protein controls biophysical properties and subcellular distribution of neuronal voltage-gated Na(+) (Nav) channels through direct binding to the channel C terminus. To gain insights into the dynamic regulation of this protein/protein interaction complex, we employed the split luciferase complementation assay to screen a small molecule library of kinase inhibitors against the FGF14·Nav1.6 channel complex and identified inhibitors of GSK3 as hits. Through a combination of a luminescence-based counter-screening, co-immunoprecipitation, patch clamp electrophysiology, and quantitative confocal immunofluorescence, we demonstrate that inhibition of GSK3 reduces the assembly of the FGF14·Nav channel complex, modifies FGF14-dependent regulation of Na(+) currents, and induces dissociation and subcellular redistribution of the native FGF14·Nav channel complex in hippocampal neurons. These results further emphasize the role of FGF14 as a critical component of the Nav channel macromolecular complex, providing evidence for a novel GSK3-dependent signaling pathway that might control excitability through specific protein/protein interactions.