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.