C. elegans CED-1 acts in neurons to modulate ciliary protein abundance and extracellular vesicle shedding

The C. elegans receptor CED-1, along with orthologs mammalian MEGF10 and Drosophila Draper, plays a well-established and conserved role in phagocytosis by acting in engulfing cells. ^1–7 Interestingly, CED-1 family members are also expressed in neurons, but their functions in these non-engulfing cells remain unclear. ^6,8,9 Our study shows that CED-1 localizes to the dendrites and primary cilia of male tail RnB neurons, which mediate sensory perceptions during mating ¹⁰ and generate extracellular vesicles (EVs) that transfer bioactive macromolecules for both intercellular and animal-to-animal communication. ¹¹ Loss of ced-1 leads to a reduction in the shedding of EVs that contain the transient receptor potential (TRP) channel PKD-2 from the cilium distal tip, and this is rescued by the expression of CED-1 in the neurons. CED-1 is required to increase both the abundance of PKD-2 in the cilium and PKD-2 EV shedding in response to the physiological stimulus of mating partners. Assessment of ced-1 mutant male mating indicates that neuronal CED-1 is also important for turning behavior, which helps the male tail to maintain contact with a mate. Collectively, these results reveal a new role for CED-1 in neurons as a regulator of EV biogenesis in response to environmental cues, optimizing the shedding of bioactive EVs for effective communication.