The dg2 (for) gene confers a renal phenotype in Drosophila by modulation of cGMP-specific phosphodiesterase.

Fluid transport in Drosophila melanogaster tubules is regulated by guanosine 3',5'-cyclic monophosphate (cGMP) signalling. Here we compare the functional effects on tubules of different alleles of the dg2 (foraging or for) gene encoding a cGMP-dependent protein kinase (cGK), and show that the fors allele confers an epithelial phenotype. This manifests itself as hypersensitivity of epithelial fluid transport to the nitridergic neuropeptide, capa-1, which acts through nitric oxide and cGMP. However, there was no significant difference in tubule cGK activity between fors and forR adults. Nonetheless, fors tubules contained higher levels of cGMP-specific phosphodiesterase (cG-PDE) activity compared to forR. This increase in cGMP-PDE activity sufficed to decrease cGMP content in fors tubules compared to forR. Challenge of tubules with capa-1 increases cGMP content in both fors and forR tubules, although the increase from resting cGMP levels is greater in fors tubules. Capa-1 stimulation of tubules reveals a potent inhibition of cG-PDE in both lines, although this is greater in fors; and is sufficient to explain the hypersensitive transport phenotype observed. Thus, polymorphisms at the dg2 locus do indeed confer a cGMP-dependent transport phenotype, but this can best be ascribed to an indirect modulation of cG-PDE activity, and thence cGMP homeostasis, rather than a direct effect on cGK levels.