title: The dg2 (for) gene confers a renal phenotype in Drosophila by modulation of cGMP-specific phosphodiesterase.
abstract: 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.
authors.affiliation: Institute of Biomedical and Life Sciences, Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, UK.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: MacPherson
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick
authors.forename: Shirley
authors.initials: S
authors.lastname: Graham
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Day
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
authors.forename: Julian A T
authors.initials: JA
authors.lastname: Dow
authors.forename: Shireen A
authors.initials: SA
authors.lastname: Davies
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D008124:Locomotion / Q000235:genetics; D008317:Malpighian Tubules / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D009479:Neuropeptides; C455043:capa protein, Drosophila; D017869:Cyclic GMP-Dependent Protein Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP