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A role for dZIP89B in Drosophila dietary zinc uptake reveals additional complexity in the zinc absorption process


Richards, CD and Warr, CG and Burke, R, A role for dZIP89B in Drosophila dietary zinc uptake reveals additional complexity in the zinc absorption process, International Journal of Biochemistry and Cell Biology, 69 pp. 11-19. ISSN 1357-2725 (2015) [Refereed Article]

DOI: doi:10.1016/j.biocel.2015.10.004


Dietary zinc is the principal source of zinc in eukaryotes, with its uptake and distribution controlled by a complex network of numerous membrane-spanning transport proteins. Dietary absorption is achieved by members of the SLC39A (ZIP) gene family, which encode proteins that are generally responsible for the movement of zinc into the cytosol. ZIP4 is thought to be the primary mammalian zinc uptake gene in the small intestine, with mutations in this gene causing the zinc deficiency disease Acrodermatitis enteropathica. In Drosophila, dual knockdown of the major dietary zinc uptake genes dZIP42C.1 (dZIP1) and dZIP42C.2 (dZIP2) results in a severe sensitivity to zinc-deficient media. However, the symptoms associated with ZIP4 loss can be reversed by zinc supplementation and dZIP42C.1 and 2 knockdown has minimal effect under normal dietary conditions, suggesting that additional pathways for zinc absorption exist in both mammals and flies. This study provides evidence that dZIP89B is an ideal candidate for this role in Drosophila, encoding a low-affinity zinc uptake transporter active in the posterior midgut. Flies lacking dZIP89B, while viable and apparently healthy, show indications of low midgut zinc levels, including reduced metallothionein B expression and compensatory up-regulation of dZIP42C.1 and 2. Furthermore dZIP89B mutants display a dramatic resistance to toxic dietary zinc levels which is abrogated by midgut-specific restoration of dZIP89B activity. We postulate that dZIP89B works in concert with the closely related dZIP42C.1 and 2 to ensure optimal zinc absorption under a range of dietary conditions. © 2015 Elsevier Ltd. All rights reserved.

Item Details

Item Type:Refereed Article
Keywords:Drosophila; dZIP89B; Ion transport; Zinc homeostasis; ZIP; metallothionein; metallothionein B; unclassified drug; zinc; zinc transporter; cation transport protein; Drosophila protein; dZIP89B protein, Drosophila; enhanced green fluorescent protein
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
ID Code:131335
Year Published:2015
Web of Science® Times Cited:10
Deposited By:Medicine
Deposited On:2019-03-13
Last Modified:2019-03-13

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