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.

本研究采用共聚焦成像技术，探究了AIS蛋白组成和神经元放电在特定激酶抑制剂针对AKT/GSK3通路的作用下的变化情况。该通路先前已被证实能够磷酸化选择性的AIS蛋白。通过对电压门控钠离子通道（Nav）、ankyrinG、βIV型肌动蛋白和细胞粘附分子神经丝的细胞模式分布进行图像特征分析，研究揭示了βIV型肌动蛋白是AKT/GSK3通路下游的一个汇聚靶点，AKT抑制剂三西里宾通过增加βIV肌动蛋白在AIS区域的定位并改变其在神经元内的极性分布，从而影响了其定位。