A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity

Zinc absorption in animals is thought to be regulated in a local, cell autonomous manner with intestinal cells responding to dietary zinc content. The <em>Drosophila</em> zinc transporter Zip88E shows strong sequence similarity to Zips 42C.1, 42C.2 and 89B as well as mammalian Zips 1, 2 and 3, suggesting that it may act in concert with the apically-localised <em>Drosophila</em> zinc uptake transporters to facilitate dietary zinc absorption by importing ions into the midgut enterocytes. However, the functional characterisation of <em>Zip88E</em> presented here indicates that <em>Zip88E</em> may instead play a role in detecting and responding to zinc toxicity. Larvae homozygous for a null <em>Zip88E</em> allele are viable yet display heightened sensitivity to elevated levels of dietary zinc. This decreased zinc tolerance is accompanied by an overall decrease in <em>Metallothionein B</em> transcription throughout the larval midgut. A <em>Zip88E</em> reporter gene is expressed only in the salivary glands, a handful of enteroendocrine cells at the boundary between the anterior and middle midgut regions, and in two parallel strips of sensory cell projections connecting to the larval ventral ganglion. <em>Zip88E</em> expression solely in this restricted subset of cells is sufficient to rescue the <em>Zip88E</em> mutant phenotype. Together, our data suggest that <em>Zip88E</em> may be functioning in a small subset of cells to detect excessive zinc levels and induce a systemic response to reduce dietary zinc absorption and hence protect against toxicity.