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

被引:53
作者
Evans, Jennifer M. [1 ]
Day, Jonathan P. [1 ]
Cabrero, Pablo [1 ]
Dow, Julian A. T. [1 ]
Davies, Shireen-Anne [1 ]
机构
[1] Univ Glasgow, Fac Biomed & Life Sci, Div Mol Genet, Glasgow G11 6NU, Lanark, Scotland
基金
英国生物技术与生命科学研究理事会;
关键词
malpighian tubule; functional genomics; cyclic nucleotide; transporters; ABCC; ABCG;
D O I
10.1242/jeb.014837
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:890 / 899
页数:10
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