Cilia function is associated with axon initial segment morphology.

ABSTRACT

Cilia, as key integrators of extracellular ligand-based signaling, play a critical role in signaling in the neuronal system. However, the function of cilia in neurons is largely unknown. In this study, we discovered that cilia morphology and ciliary protein localization were associated with axon initial segment (AIS) morphology, including length and location. Cilia morphological changes induced by the serotonin (5-HT) receptor 5-HT6R, intraflagellar transport 88 (Ift88) and kinesin family member 3A (KIF3A) altered AIS length and location. The change in cilia morphology was associated with aberrant localization of ankyrin G (AnkG) and voltage-gated sodium channel 1.2 (Nav1.2). Cilia morphology altered action potential (AP) amplitude and spike firing. Taken together, our data strongly suggest that cilia function might have a marked impact on neuron excitability by regulating AIS morphology and ion channel localization. Our findings highlight a novel aspect linking cilia function and neuron excitability.