Abstract
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.
Highlights
Zinc is an essential dietary nutrient, required as a structural or enzymatic cofactor for potentially thousands of different proteins
Zinc transporter Zip88E protects against zinc toxicity direction, removing zinc from the cell or supplying organelles such as the endoplasmic reticulum, Golgi and lysosome
Zinc transporter Zip88E protects against zinc toxicity absorption in the fly
Summary
Zinc is an essential dietary nutrient, required as a structural or enzymatic cofactor for potentially thousands of different proteins. It has been estimated that up to 10% of all human proteins are able to bind zinc [1]. There is a growing body of evidence that unbound zinc ions may be able to act as signalling molecules to regulate cellular processes such as growth and neurotransmission [2]. Movement of zinc ions across cell membranes is facilitated by two large classes of proteins. Members of the Zip family have mostly been shown to transport zinc into the cytosol, either from outside the cell (cellular uptake) or from the lumen of cellular organelles in order to redistribute zinc within individual cells. ZnT proteins mostly function in the opposite
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