Receptor-induced activation of Drosophila TRPγ by polyunsaturated fatty acids

Cellular calcium homeostasis is regulated by hormones and neurotransmitters, resulting in the activation of a variety of proteins, in particular, channel proteins of the plasma membrane and of intracellular compartments. Such channels are, for example, TRP channels of the TRPC protein family that are activated by various mediators from receptor-stimulated signaling cascades. In Drosophila, two TRPC channels, TRP and TRPL, are involved in phototransduction. In addition, a third Drosophila TRPC channel, TRPγ, has been identified and described as an auxiliary subunit of TRPL. Beyond it, our data show that heterologously expressed TRPγ formed a receptor-activated, outwardly rectifying cation channel independent from TRPL co-expression. Analysis of the activation mechanism revealed that TRPγ is activated by various polyunsaturated fatty acids generated in a phospholipase C- and phospholipase A₂-dependent manner. The most potent activator of TRPγ, the stable analogue of arachidonic acid, 5,8,11,14-eicosatetraynoic acid, induced currents in single channel recordings. Here we show that upon heterologous expression TRPγ forms a homomeric channel complex that is activated by polyunsaturated fatty acids as mediators of receptor-dependent signaling pathways. Reverse transcription PCR analysis showed that TRPγ is expressed in Drosophila heads and bodies. Its body-wide expression pattern and its activation mechanism suggest that TRPγ forms a fly cation channel responsible for the regulation of intracellular calcium in a variety of hormonal signaling cascades.