Drosophila TRPM channel is essential for the control of extracellular magnesium levels

The TRPM group of cation channels plays diverse roles ranging from sensory signaling to Mg²⁺ homeostasis. In most metazoan organisms the TRPM subfamily is comprised of multiple members, including eight in humans. However, the Drosophila TRPM subfamily is unusual in that it consists of a single member. Currently, the functional requirements for this channel have not been reported. Here, we found that the Drosophila TRPM protein was expressed in the fly counterpart of mammalian kidneys, the Malpighian tubules, which function in the removal of electrolytes and toxic components from the hemolymph. We generated mutations in trpm and found that this resulted in shortening of the Malpighian tubules. In contrast to all other Drosophila trp mutations, loss of trpm was essential for viability, as trpm mutations resulted in pupal lethality. Supplementation of the diet with a high concentration of Mg²⁺ exacerbated the phenotype, resulting in growth arrest during the larval period. Feeding high Mg²⁺ also resulted in elevated Mg²⁺ in the hemolymph, but had relatively little effect on cellular Mg²⁺. We conclude that loss of Drosophila trpm leads to hypermagnesemia due to a defect in removal of Mg²⁺ from the hemolymph. These data provide the first evidence for a role for a Drosophila TRP channel in Mg²⁺ homeostasis, and underscore a broad and evolutionarily conserved role for TRPM channels in Mg²⁺ homeostasis.