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Zinc absorption in animals is thought to be regulated in a local, cell autonomous manner with intestinal cells responding to dietary zinc content. The  Drosophila  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  Drosophila  zinc uptake transporters to facilitate dietary zinc absorption by importing ions into the midgut enterocytes. However, the functional characterisation of  Zip88E  presented here indicates that  Zip88E  may instead play a role in detecting and responding to zinc toxicity. Larvae homozygous for a null  Zip88E  allele are viable yet display heightened sensitivity to elevated levels of dietary zinc. This decreased zinc tolerance is accompanied by an overall decrease in  Metallothionein B  transcription throughout the larval midgut. A  Zip88E  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.  Zip88E  expression solely in this restricted subset of cells is sufficient to rescue the  Zip88E  mutant phenotype. Together, our data suggest that  Zip88E  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.

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