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

Abstract

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 mating10 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.