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First published online July 2, 2004
Journal of Experimental Biology 207, 2769-2776 (2004)
Published by The Company of Biologists 2004
doi: 10.1242/jeb.01086

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

Matthew R. MacPherson^1,*, Kate E. Broderick^1,*, Shirley Graham¹, Jonathan P. Day¹, Miles D. Houslay², Julian A. T. Dow¹ and Shireen A. Davies^1,

¹ Institute of Biomedical and Life Sciences, Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, UK
² Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G11 6NU, UK

Author for correspondence (e-mail: s.a.davies{at}bio.gla.ac.uk)

Accepted 12 May 2004

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 for^s 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 for^s and for^R adults. Nonetheless, for^s tubules contained higher levels of cGMP-specific phosphodiesterase (cG-PDE) activity compared to for^R. This increase in cGMP-PDE activity sufficed to decrease cGMP content in for^s tubules compared to for^R. Challenge of tubules with capa-1 increases cGMP content in both for^s and for^R tubules, although the increase from resting cGMP levels is greater in for^s tubules. Capa-1 stimulation of tubules reveals a potent inhibition of cG-PDE in both lines, although this is greater in for^s; 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.

Key words: Malpighian tubule, cyclic nucleotide, capa-1, epithelial transport, Drosophila melanogaster, dg2 locus

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