title: In vivo zinc toxicity phenotypes provide a sensitized background that suggests zinc transport activities for most of the Drosophila               Zip and ZnT genes.
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.
authors: School of Biological Sciences, Monash University, Wellington Rd, Clayton, VIC, 3800, Australia.
authors: Jessica C
authors: JC
authors: Lye
authors: Christopher D
authors: CD
authors: Richards
authors: Kesang
authors: K
authors: Dechen
authors: Coral G
authors: CG
authors: Warr
authors: Richard
authors: R
authors: Burke
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000378:metabolism; D017136:Ion Transport; D010641:Phenotype; D034622:RNA Interference; D015854:Up-Regulation; D015032:Zinc / Q000378:metabolism* / Q000633:toxicity*
chemical_list: D027682:Cation Transport Proteins; D029721:Drosophila Proteins; D015032:Zinc