KLP-7/Kinesin-13 orchestrates axon-dendrite checkpoints for polarized trafficking in neurons

Abstract

Neurons are compartmentalized cells with spatiotemporal distinction of anatomy and molecular repertoire. Microtubule organization in the neuron is crucial for its polarized structure and composition. Microtubule dynamics are differentially optimized in the axons and dendrites by the interplay between the microtubule-stabilizing and destabilizing factors. It is unclear how the destabilizing factors are important for developing and maintaining neuronal polarity. We investigated the function of KLP-7, a microtubule depolymerizing motor from the Kinesin-13 family, in the compartmentalization of axons and dendrites using the PVD neurons in Caenorhabditis elegans. In the absence of KLP-7, axonal proteins such as RAB-3 and SAD-1 were mislocalized to dendrites, suggesting a disruption in axon-dendrite compartmentalization. Notably, this phenomenon was independent of other depolymerizing factors like EFA-6, highlighting the specific role of KLP-7 in this process. We observed a reduced rate of microtubule polymerization and an altered polarity of microtubules in the PVD major dendrite due to the loss of klp-7. Additionally, the deletion of klp-7 led to the formation of ectopic neurites from the cell body and the ectopic localization of UNC-44/Ankyrin-G, a protein associated with the axon initial segment (AIS), to the dendrites. Additionally, live imaging of GFP::KLP-7 revealed that KLP-7 is more dynamic in the dendrites as compared to the axon. These observations indicate that the precise dynamics of KLP-7 in neurites are crucial for maintaining distinct microtubule polymerization in the axons and dendrites, thereby influencing neuronal polarity. Our findings shed light on the pivotal role of KLP-7/Kinesin-13 in the establishment of axon-dendrite checkpoints, which in turn impact the polarized trafficking of cellular components within neurons.