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In vivo zinc toxicity phenotypes provide a sensitized background that suggests zinc transport activities for most of the Drosophila Zip and ZnT genes

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Abstract

Members of the ZIP (SLC39A) and ZnT (SLC30A) families of transmembrane domain proteins are predicted to transport the essential transition metal zinc across membranes, regulating cellular zinc content and distribution via uptake and efflux at the outer plasma and organellar membranes. Twenty-four ZIP and ZnT proteins are encoded in mammalian genomes, raising questions of whether all actually transport zinc, whether several function together in the same tissues/cell types, and how the activity of these transporters is coordinated. To address these questions, we have taken advantage of the ability to manipulate several genes simultaneously in targeted cell types in Drosophila. Previously we reported zinc toxicity phenotypes caused by combining overexpression of a zinc uptake gene, dZip42C.1, with suppression of a zinc efflux gene, dZnT63C. Here we show that these phenotypes can be used as a sensitized in vivo system to detect subtle alterations in zinc transport activity that would be buffered in healthy cells. Using two adult tissues, the fly eye and midline (thorax/abdomen), we find that when overexpressed, most of the 17 Drosophila Zip and ZnT genes modify the zinc toxicity phenotypes in a manner consistent with their predicted zinc transport activity. In most cases, we can reconcile that activity with the cellular localization of an enhanced green fluorescent protein tagged version of the protein. Additionally, targeted suppression of each gene by RNA interference reveals several of the fly Zip and ZnT genes are required in the eye, indicating that numerous independent zinc transport genes are acting together in a single tissue.

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Acknowledgments

Drosophila stocks were imported into Australia by the Australian Drosophila Biomedical Research Support Facility (http://www.ozdros.com). All Drosophila RNAi lines were provided by the Vienna Drosophila RNAi Center. Confocal microscopy was done at Monash Micro Imaging, which also provided training and technical support. This research was supported by a project grant (grant number 606609) from the Australian National Health and Medical Research Council.

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Authors and Affiliations

  1. School of Biological Sciences, Monash University, Wellington Rd, Clayton, VIC, 3800, Australia

    Jessica C. Lye, Christopher D. Richards, Kesang Dechen, Coral G. Warr & Richard Burke

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  1. Jessica C. Lye
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  2. Christopher D. Richards
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  3. Kesang Dechen
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  4. Coral G. Warr
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  5. Richard Burke
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Correspondence to Richard Burke.

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Lye, J.C., Richards, C.D., Dechen, K. et al. In vivo zinc toxicity phenotypes provide a sensitized background that suggests zinc transport activities for most of the Drosophila Zip and ZnT genes. J Biol Inorg Chem 18, 323–332 (2013). https://doi.org/10.1007/s00775-013-0976-6

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  • DOI: https://doi.org/10.1007/s00775-013-0976-6

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