Title:

Role of cyclic nucleotide phosphodiesterases in chemosensation of the nematode C. elegans

Over 4,000 species of plant parasitic nematodes have a serious impact on global food security, with ~$100B in crop damages annually. Nematode behavior and lifecycle depend on cyclic nucleotide signaling. Phosphodiesterases (PDEs) are major determinants of cellular levels of cyclic nucleotides because they are solely responsible for lowering intracellular levels of the cyclic nucleotide second messengers, cAMP and cGMP. However, there is limited knowledge of the role of individual PDEs in mediating nematode signalling pathways. Mammals possess 11 PDE families (PDE1-PDE11), whereas nematodes have PDE genes representing six families. Using the free-living nematode C. elegans to generate transgenic strains lacking individual PDE genes, we show that ablating pde-1 abolished chemosensation to two attractant compounds (2-butanone and isoamyl alcohol) and a repellent compound (1-octanol). To mimic the phenotype observed in this pde-1 “knock-out” strain, we found that exposure of wild-type C. elegans (N2 strain) to a human PDE1- specific inhibitor also reduced the chemotactic response to the 2-butanone. This nematode PDE family may be a future target for the development of chemical nematicides that disrupt the ability of parasitic nematodes to identify and invade their host. This work supports the feasibility of designing nematicidal compounds targeting specific parasitic nematode PDEs lacking adverse effects on vertebrate animals or agricultural crops.

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