Genetic determinants of phosphate response in Drosophila

• Published in: PloS one 2013-03, Vol.8 (3), p.e56753-e56753
• Main Authors: Bergwitz, Clemens, Wee, Mark J, Sinha, Sumi, Huang, Joanne, DeRobertis, Charles, Mensah, Lawrence B, Cohen, Jonathan, Friedman, Adam, Kulkarni, Meghana, Hu, Yanhui, Vinayagam, Arunachalam, Schnall-Levin, Michael, Berger, Bonnie, Perkins, Lizabeth A, Mohr, Stephanie E, Perrimon, Norbert
• Format: Article
• Language: English
• Subjects: Acids; Activation; Aging; Analysis; Anemia; Animals; Artificial intelligence; Biology; Cell Line; Computer science; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Flies; Gene expression; Genes; Genetic aspects; Genetics; Genomes; Genomics; Growth factors; Hemocytes - metabolism; Hemolymph; Hemolymph - metabolism; Hormones; Insects; Kinases; Larval development; Life span; Longevity - drug effects; Longevity - physiology; Malpighian tubules; Malpighian Tubules - metabolism; Mammals; MAP kinase; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Medical schools; Medicine; Metabolism; Oxidative stress; Phosphate; Phosphate esters; Phosphates; Phosphates - metabolism; Phosphates - pharmacology; Raf protein; RNA Interference; RNA-mediated interference; Signal transduction; Signaling; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056753

Phosphate is required for many important cellular processes and having too little phosphate or too much can cause disease and reduce life span in humans. However, the mechanisms underlying homeostatic control of extracellular phosphate levels and cellular effects of phosphate are poorly understood. Here, we establish Drosophila melanogaster as a model system for the study of phosphate effects. We found that Drosophila larval development depends on the availability of phosphate in the medium. Conversely, life span is reduced when adult flies are cultured on high phosphate medium or when hemolymph phosphate is increased in flies with impaired malpighian tubules. In addition, RNAi-mediated inhibition of MAPK-signaling by knockdown of Ras85D, phl/D-Raf or Dsor1/MEK affects larval development, adult life span and hemolymph phosphate, suggesting that some in vivo effects involve activation of this signaling pathway by phosphate. To identify novel genetic determinants of phosphate responses, we used Drosophila hemocyte-like cultured cells (S2R+) to perform a genome-wide RNAi screen using MAPK activation as the readout. We identified a number of candidate genes potentially important for the cellular response to phosphate. Evaluation of 51 genes in live flies revealed some that affect larval development, adult life span and hemolymph phosphate levels.