title: NIP/DuoxA is essential for Drosophila embryonic development and regulates oxidative stress response.
abstract: NIP/DuoxA, originally cloned as a protein capable of binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS) production in mammalian systems. Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox) enzyme, the in vivo function of NIP/DuoxA has not been characterized to date. Here we report a genetic and functional characterization of nip in Drosophila melanogaster. We show that nip is essential for Drosophila development as nip null mutants die at the 1(st) larval instar. Expression of UAS-nip, but not UAS-Duox, rescued the lethality. To understand the function of nip beyond the early larval stage, we generated GAL4 inducible UAS-RNAi transgenes. da(G32)-GAL4 driven, ubiquitous RNAi-mediated silencing of nip led to profound abnormality in pre-adult development, crinkled wing and markedly reduced lifespan at 29 degrees C. Compared to wild type flies, da-GAL4 induced nip-RNAi transgenic flies exhibited significantly reduced ability to survive under oxidative stress and displayed impaired mitochondrial aconitase function. Our work provides in vivo evidence for a critical role for nip in the development and oxidative stress response in Drosophila.
authors.affiliation: Department of Biochemistry and the Siebens-Drake Medical Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xie
authors.forename: Jack
authors.initials: J
authors.lastname: Hu
authors.forename: Xiping
authors.initials: X
authors.lastname: Liu
authors.forename: Hanjuan
authors.initials: H
authors.lastname: Qin
authors.forename: Anthony
authors.initials: A
authors.lastname: Percival-Smith
authors.forename: Yong
authors.initials: Y
authors.lastname: Rao
authors.forename: Shawn S C
authors.initials: SS
authors.lastname: Li
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics; D007814:Larva / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D019076:Transgenes; D014921:Wings, Animal / Q000378:metabolism
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species