title: Syntaxin 5 is required for copper homeostasis in Drosophila and mammals.
abstract: Copper is essential for aerobic life, but many aspects of its cellular uptake and distribution remain to be fully elucidated. A genome-wide screen for copper homeostasis genes in Drosophila melanogaster identified the SNARE gene Syntaxin 5 (Syx5) as playing an important role in copper regulation; flies heterozygous for a null mutation in Syx5 display increased tolerance to high dietary copper. The phenotype is shown here to be due to a decrease in copper accumulation, a mechanism also observed in both Drosophila and human cell lines. Studies in adult Drosophila tissue suggest that very low levels of Syx5 result in neuronal defects and lethality, and increased levels also generate neuronal defects. In contrast, mild suppression generates a phenotype typical of copper-deficiency in viable, fertile flies and is exacerbated by co-suppression of the copper uptake gene Ctr1A. Reduced copper uptake appears to be due to reduced levels at the plasma membrane of the copper uptake transporter, Ctr1. Thus Syx5 plays an essential role in copper homeostasis and is a candidate gene for copper-related disease in humans.
authors.affiliation: School of Biological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Norgate
authors.forename: Adam
authors.initials: A
authors.lastname: Southon
authors.forename: Mark
authors.initials: M
authors.lastname: Greenough
authors.forename: Michael
authors.initials: M
authors.lastname: Cater
authors.forename: Ashley
authors.initials: A
authors.lastname: Farlow
authors.forename: Philip
authors.initials: P
authors.lastname: Batterham
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: V Nathan
authors.initials: VN
authors.lastname: Subramaniam
authors.forename: Richard
authors.initials: R
authors.lastname: Burke
authors.forename: James
authors.initials: J
authors.lastname: Camakaris
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D000079922:Copper Transport Proteins; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics; D006579:Heterozygote; D006706:Homeostasis; D006801:Humans; D008322:Mammals; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; C559059:Ctr1A protein, Drosophila; C550077:Ctr1C protein, Drosophila; D029721:Drosophila Proteins; D050765:Qa-SNARE Proteins; D003300:Copper