Molecular dissection of tyraminergic communication in the Drosophila Malpighian tubule

The biogenic amine tyramine (TA) acts as a diuretic agent in the Drosophila Malpighian tubule (MT), increasing urine secretion by activating a transepithelial chloride conductance. The MT can also synthesize TA when its precursor, L‐tyrosine, is present in the peritubular fluid. The goal of this study was to identify two of the gene products necessary for TA signaling: tyrosine decarboxylase (tdc), the enzyme that converts tyrosine to TA, and the TA receptor (TAR). The Drosophila genome contains two tdc genes: tdc1 and tdc2 (Cole et al., 2005). The tdc1 gene is highly expressed in the MT while tdc2 is not. MTs from tdc1 mutant flies show no electrophysiological or diuretic responses to tyrosine but normal responses to TA; in contrast, mutation of tdc2 does not alter tyrosine sensitivity. Overexpressing tdc1 in the principal cells, but not the stellate cells, of tdc1 mutants, rescues tyrosine sensitivity, suggesting that TA synthesis occurs in the principal cells. The TAR in the MT is unlikely to be encoded by the canonical TAR gene tyrR , which is expressed in the MT at very low levels. In contrast, the recently identified TAR gene CG7431 (Cazzamali et al., 2005) is abundantly expressed in the MT. Mutation of CG7431 results in complete insensitivity to TA, suggesting that CG7431 encodes the TAR in the MT. Rescue experiments are underway to determine the cell type in which this receptor functions. Supported by Marquette University