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Identification of the tyramine receptor in the Drosophila Malpighian tubule

The Malpighian tubule of Drosophila is the most well‐characterized system available for studying the cellular actions of the biogenic amine tyramine (TA) in insects. In isolated tubules, application of TA causes a rapid increase in transepithelial chloride conductance that is easily measured electrophysiologically (Blumenthal, AJP Cell, 2003). One major outstanding question regarding this system is the identity of the receptor for TA. Although a TA receptor (tyrR) has been cloned from Drosophila and many other insect species, the expression of this gene in the tubules is exceptionally low and unlikely to be physiologically relevant. Recently, the gene CG7431 has been reported to form a TA‐specific receptor when expressed in heterologous systems (Cazzamali, Klaerke, and Grimmelikhuijzen, BBRC, in press). We find that CG7431 is expressed in the tubules at levels 100–200 fold higher than that of the tyrR gene. We have obtained a line of flies containing a transposon insertion in the CG7431 gene. Tubules from these flies have an extremely low sensitivity to TA; wild‐type tubules give a threshold response at 1 nM TA and a near‐maximal response at 100 nM, while mutant tubules display a threshold response at approximately 1000 nM TA. We are currently working to determine if TA sensitivity is restored upon excision of the transposon. Based on our expression and physiological data and on the published heterologous expression data, we tentatively conclude that CG7431 encodes the primary TA receptor in the Malpighian tubules.