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bioRxiv · 10.1101/2024.02.15.580526

UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.

Drozd, C. J.·Chowdhury, T. A.·Quinn, C. C.
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Abstract

MAPK8IP3 (unc-16/JIP3) is a neurodevelopmental-disorder associated gene that can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16 promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16 function causes accumulation of late endosomes specifically in the distal axon. Moreover, we observe synergistic interactions between loss of unc-16 function and disruptors of endolysosomal function, indicating that the endolysosomal system promotes axon termination. We also find that the axon termination defects caused by loss of UNC-16 function require the function of a genetic pathway that includes lrk-1 and wdfy-3, two genes that have been implicated in autophagy. These observations suggest a model where UNC-16 promotes axon termination by interacting with the endolysosomal system to regulate a pathway that includes LRK-1 and WDFY-3.

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Drozd, C. J., Chowdhury, T. A., Quinn, C. C.. 2024-02-16. UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.. https://doi.org/10.1101/2024.02.15.580526

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