Natural isolates of C. elegans exhibit either social or solitary feeding behaviour. Animals from social strains, such as the Hawaiian strain CB4856, aggregate and feed in groups on a bacterial lawn. In contrast, well-fed animals from solitary strains, such as N2, feed alone. This behavioural variation is associated with a single amino acid polymorphism in NPR-1, a FaRP neuropeptide receptor (see abstract by C. Rogers et al.). Null mutations in
npr-1 transform solitary wild strains into strongly social animals, indicating that
npr-1 suppresses social feeding. To define molecules required for social feeding, we mutagenized
npr-1(null) social animals and selected mutants that feed alone. Five of the X-linked mutations we identified failed to complement one another and mapped to a 50kb interval close to
lin-15. All five alleles strongly suppressed aggregation behaviour, but showed little or no other behavioural defects. Transgenic rescue experiments and sequencing data revealed that these alleles all disrupt
gcy-36, one of the seven worm homologues of human soluble guanylate cyclase (sGC)1. In mammals, sGCs are involved in neuronal signalling, axon guidance and maintenance of vascular tone, and are activated by nitric oxide. Since no nitric oxide synthase has been found in the worm genome, C. elegans sGCs are likely regulated by a different mechanism 1. Transgenic studies suggest that the cGMP-gated ion channel subunit TAX-4 is required in one or more of the body cavity neurones AQR, PQR and URX for social feeding behaviour 2. These neurones directly contact the body fluid, and appear to integrate antagonistic signals to control social behaviour2. David Karow in the Marletta lab has shown that
gcy-36 is expressed in AQR, PQR and URX 3. Several
gcy-36 expression constructs we have made confirmed this earlier result. To show that
gcy-36 is required in the body cavity neurones for social feeding, we expressed
gcy-36 cDNA from the
gcy-32 promoter, which drives expression in AQR, PQR and URX 4, and from the
flp-8 promoter, which expresses in AUA and URX 5. Both constructs restored strong social feeding to
npr-1 gcy-36 mutant animals. These data suggest that signalling from a soluble guanylate cyclase in the URX neurones activates the TAX-4/TAX-2 cGMP-gated channel to induce social feeding. 1 Morton et al., 1999, Current Biology, 9, R546-547; 2 Coates and de Bono, 2002, Nature 419:925-929; 3 D. Karow et al., WCWM 2002, Abst. 237; 4 Yu et al., 1997, PNAS, 94:3384-3387; 5 Chris Li, pers. com.