Reference Report

Reference
Citation	Day, J.P., Houslay, M.D., Davies, S.A. (2006). A novel role for a Drosophila homologue of cGMP-specific phosphodiesterase in the active transport of cGMP. Biochem. J. 393(2): 481--488. (Export to RIS)
FlyBase ID	FBrf0189812
Publication Type	Research paper
PubMed ID	16232123
PubMed Abstract	cGMP was first discovered in urine, demonstrating that kidney cells extrude this cyclic nucleotide. Drosophila Malpighian tubules provide a model renal system in which a homologue of mammalian PDE (phosphodiesterase) 6 is expressed. In humans, this cG-PDE (cGMP-specific PDE) is specifically expressed in the retinal system, where it controls visual signal transduction. In order to gain insight into the functional role of DmPDE6 (Drosophila PDE6-like enzyme) in epithelial function, we generated transgenic animals with targeted expression of DmPDE6 to tubule Type I (principal) cells. This revealed localization of DmPDE6 primarily at the apical membranes. As expected, overexpression of DmPDE6 resulted in elevated cG-PDE activity and decreased tubule cGMP content. However, such targeted overexpression of DmPDE6 creates a novel phenotype that manifests itself in inhibition of the active transport and efflux of cGMP by tubules. This effect is specific to DmPDE6 action, as no effect on cGMP transport is observed in tubules from a bovine PDE5 transgenic line which display reduced rates of fluid secretion, an effect not seen in DmPDE6 transgenic animals. Specific ablation of DmPDE6 in tubule principal cells, via expression of a targeted DmPDE6 RNAi (RNA interference) transgene, conferred increased active transport of cGMP, confirming a direct role for DmPDE6 in regulating cGMP transport in tubule principal cells. Pharmacological inhibition of DmPDE6 in wild-type tubules using the cG-PDE inhibitor, zaprinast, similarly results in stimulated cGMP transport. We provide the first demonstration of a novel role for a cG-PDE in modulating cGMP transport and efflux.
DOI
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Biochem. J.
Title	The Biochemical Journal
Publication Year	1906-
ISBN/ISSN	0264-6021
Data from Reference
Alleles (8)
	Btau\PDE5A^Scer\UAS.cBa Pde6^{dsRNA.Scer\UAS.cDa} Pde6^{Scer\UAS.T:Avic\GFP-EGFP} Scer\GAL4^Act.PU Scer\GAL4^c42 Scer\GAL4^da.G32 T:Avic\GFP^EGFP w^+mC
Constructs (5)
	P{Act-GAL4.U} P{GAL4-da.G32} P{UAS-PDE5A.B} P{UAS-Pde6.EGFP} P{UAS-Pde6.RNAi.D}
Genes (4)
	Btau\PDE5A Pde6 Scer\GAL4 w
Insertions (1)
	P{GawB}c42
Natural transposons (1)
	P-element