title: Genetic determinants of phosphate response in Drosophila.
abstract: 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.
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America. cwhb2002@yahoo.com
authors.forename: Clemens
authors.initials: C
authors.lastname: Bergwitz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Wee
authors.forename: Sumi
authors.initials: S
authors.lastname: Sinha
authors.forename: Joanne
authors.initials: J
authors.lastname: Huang
authors.forename: Charles
authors.initials: C
authors.lastname: DeRobertis
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Mensah
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.forename: Adam
authors.initials: A
authors.lastname: Friedman
authors.forename: Meghana
authors.initials: M
authors.lastname: Kulkarni
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Vinayagam
authors.forename: Michael
authors.initials: M
authors.lastname: Schnall-Levin
authors.forename: Bonnie
authors.initials: B
authors.lastname: Berger
authors.forename: Lizabeth A
authors.initials: LA
authors.lastname: Perkins
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Mohr
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D006434:Hemocytes / Q000378:metabolism; D006458:Hemolymph / Q000378:metabolism; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008317:Malpighian Tubules / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism* / Q000494:pharmacology; D034622:RNA Interference
chemical_list: D029721:Drosophila Proteins; D010710:Phosphates