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Systematic functional characterization of putative zinc transport genes and identification of zinc toxicosis phenotypes in Drosophila melanogaster
journal contribution
posted on 2023-05-20, 02:39 authored by Lye, JC, Richards, CD, Dechen, K, D Paterson, De Jonge, MD, Howard, DL, Coral WarrCoral Warr, Burke, RThe heavy metal zinc is an essential component of the human diet and is incorporated as a structural component in up to 10% of all mammalian proteins. The physiological importance of zinc homeostasis at the cellular level and the molecular mechanisms involved in this process have become topics of increasing interest in recent years. We have performed a systematic functional characterization of the majority of the predicted Drosophila Zip (zinc/iron regulated transporter-related protein) and ZnT genes, using the Gal4-UAS system to carry out both ubiquitous and targeted over-expression and suppression studies for 13 of the 17 putative zinc transport genes identified to date. We found that six of these 13 genes may be essential for fly viability and that three of the remaining seven demonstrate over-expression phenotypes. Our findings reaffirm the previously proposed function of dZnT63C (CG17723: FBgn005432) as an important zinc efflux protein and indicate that the fly homolog of hZip1, dZip42C.1 (CG9428: FBgn0033096), is a strong zinc importer in Drosophila. By combining over-expression of dZip42C.1 with suppression of dZnT63C we were able to produce easily identifiable zinc toxicosis phenotypes, which can be rescued or worsened by modifying dietary zinc content. Our findings show that a genetically based zinc toxicosis situation can be therapeutically treated or exacerbated by modifications to the diet, providing a sensitized background for future, more detailed studies of Zip/ZnT function.
History
Publication title
Journal of Experimental BiologyVolume
215Issue
18Pagination
3254-3265ISSN
0022-0949Department/School
Tasmanian School of MedicinePublisher
Company Of Biologists LtdPlace of publication
Bidder Building Cambridge Commercial Park Cowley Rd, Cambridge, England, Cambs, Cb4 4DlRepository Status
- Restricted