Di Re, Hsu et al Disrupted interactions of proteins at the axon initial segment induced by AKT/GSK3 kinase signaling

We used confocal imaging to study how AIS protein composition and neuronal firing varied in response to selected kinase inhibitors targeting the AKT/GSK3 pathway, which has previously been shown to phosphorylate select AIS proteins. Image-based features representing cellular pattern distribution of the voltage-gated Na+ (Nav) channel, ankyrinG, βIV spectrin, and the cell-adhesion molecule neurofascin were analyzed. Analysis revealed bIV spectrin as a converging downstream target of the AKT/GSK3 pathway with the AKT inhibitor triciribine increasing bIV Spectrin localization to the AIS and altering its polar distribution within neurons.