Cilia and extracellular vesicles (EVs) are signaling organelles [1]. Cilia act as
cellular sensory antennae, with defects resulting in human ciliopathies. Cilia both
release and bind to EVs [1]. EVs are sub-micron-sized particles released by cells
and function in both short- and long-range intercellular communication. In C. elegans
and mammals, the autosomal dominant polycystic kidney disease (ADPKD) gene products
polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic
pathway, and function in a sensory capacity, suggesting ancient conservation [2].
A fundamental understanding of EV biology and the relationship between the polycystins,
cilia, and EVs is lacking. To define properties of a ciliated EV-releasing cell, we
performed RNA-seq on 27 GFP-labeled EV-releasing neurons (EVNs) isolated from adult
C. elegans. We identified 335 significantly overrepresented genes, of which 61 were
validated by GFP reporters. The EVN transcriptional profile uncovered new pathways
controlling EV biogenesis and polycystin signaling and also identified EV cargo, which
included an antimicrobial peptide and ASIC channel. Tumor-necrosis-associated factor
(TRAF) homologs trf-1 and trf-2 and the p38 mitogen-activated protein kinase (MAPK)
pmk-1 acted in polycystin-signaling pathways controlling male mating behaviors. pmk-1
was also required for EV biogenesis, independent of the innate immunity MAPK signaling
cascade. This first high-resolution transcriptome profile of a subtype of ciliated
sensory neurons isolated from adult animals reveals the functional components of an
EVN.