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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 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 tha...

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Autores principales: Richards, Christopher D., Warr, Coral G., Burke, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509326/
https://www.ncbi.nlm.nih.gov/pubmed/28704512
http://dx.doi.org/10.1371/journal.pone.0181237
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author Richards, Christopher D.
Warr, Coral G.
Burke, Richard
author_facet Richards, Christopher D.
Warr, Coral G.
Burke, Richard
author_sort Richards, Christopher D.
collection PubMed
description 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.
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spelling pubmed-55093262017-08-07 A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity Richards, Christopher D. Warr, Coral G. Burke, Richard PLoS One Research Article 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. Public Library of Science 2017-07-13 /pmc/articles/PMC5509326/ /pubmed/28704512 http://dx.doi.org/10.1371/journal.pone.0181237 Text en © 2017 Richards et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Richards, Christopher D.
Warr, Coral G.
Burke, Richard
A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity
title A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity
title_full A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity
title_fullStr A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity
title_full_unstemmed A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity
title_short A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity
title_sort role for the drosophila zinc transporter zip88e in protecting against dietary zinc toxicity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509326/
https://www.ncbi.nlm.nih.gov/pubmed/28704512
http://dx.doi.org/10.1371/journal.pone.0181237
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