A new role for a classical gene: white transports cyclic GMP

Evans, J.M., Day, J.P., Cabrero, P., Dow, J.A.T. and Davies, S.A. (2008) A new role for a classical gene: white transports cyclic GMP. Journal of Experimental Biology, 211, pp. 890-899. (doi: 10.1242/jeb.014837) (PMID:18310115)

Abstract

Guanosine 3'-5' cyclic monophosphate (cGMP) and adenosine 3'-5' cyclic monophosphate (cAMP) are important regulators of cell and tissue function. However, cGMP and cAMP transport have received relatively limited attention, especially in model organisms where such studies can be conducted in vivo. The Drosophila Malpighian (renal) tubule transports cGMP and cAMP and utilises these as signalling molecules. We show here via substrate competition and drug inhibition studies that cAMP transport but not cGMP transport requires the presence of di- or tri-carboxylates; and that transport of both cyclic nucleotides occurs via ATP binding cassette sub-family G2 (ABCG2), but not via ABC sub-family C (ABCC), transporters. In Drosophila, the white (w) gene is known for the classic eye colour mutation. However, gene expression data show that of all adult tissues, w is most highly expressed in Malpighian tubules. Furthermore, as White is a member of the ABCG2 transporter class, it is a potential candidate for a tubule cGMP transporter. Assay of cGMP transport in w (mutant) tubules shows that w is required for cGMP transport but not cAMP transport. Targeted over-expression of w in w tubule principal cells significantly increases cGMP transport compared with that in w controls. Conversely, treatment of wild-type tubules with cGMP increases w mRNA expression levels, implying that cGMP is a physiologically relevant substrate for White. Immunocytochemical localisation reveals that White is expressed in intracellular vesicles in tubule principal cells, suggesting that White participates in vesicular transepithelial transport of cGMP

• Item Type: Articles
• Additional Information: Publisher does not allow authors to deposit full text on institutional site only personal.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dow, Professor Julian and Davies, Professor Shireen
• Authors: Evans, J.M., Day, J.P., Cabrero, P., Dow, J.A.T., and Davies, S.A.
• Subjects: Q Science > QH Natural history > QH426 Genetics
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Journal of Experimental Biology
• ISSN: 0022-0949

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
37848	1	Exploration of cyclic 3', 5' guanosine monophosphate (cGMP) signalling dynamics in vivo	Shireen Davies	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/C000633/1	Institute of Molecular Cell and Systems Biology