title: Contribution of Drosophila TRPA1 to Metabolism.
abstract: Transient receptor potential (TRP) cation channels are highly conserved in humans and insects. Some of these channels are expressed in internal organs and their functions remain incompletely understood. By direct knock-in of the GAL4 gene into the trpA1 locus in Drosophila, we identified the expression of this gene in the subesophageal ganglion (SOGs) region. In addition, the neurites present in the dorsal posterior region as well as the drosophila insulin-like peptide 2 (dILP2)-positive neurons send signals to the SOGs. The signal is sent to the crop, which is an enlarged organ of the esophagus and functions as a storage place for food in the digestive system. To systematically investigate the role of TRPA1 in metabolism, we applied non-targeted metabolite profiling analysis together with gas-chromatography/time-of-flight mass spectrometry, with an aim to identify a wide range of primary metabolites. We effectively captured distinctive metabolomic phenotypes and identified specific metabolic dysregulation triggered by TRPA1 mutation based on reconstructed metabolic network analysis. Primarily, the network analysis pinpointed the simultaneous down-regulation of intermediates in the methionine salvation pathway, in contrast to the synchronized up-regulation of a range of free fatty acids. The gene dosage-dependent dynamics of metabolite levels among wild-type, hetero- and homozygous mutants, and their coordinated metabolic modulation under multiple gene settings across five different genotypes confirmed the direct linkages of TRPA1 to metabolism.
authors.affiliation: Department of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul 02707, Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul 02707, Korea.
authors.forename: Yunjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul, Korea.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul 02707, Korea.
authors.forename: Do Yup
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Bio and Fermentation Convergence Technology, BK21 PLUS project, Kookmin University, Seoul 02707, Korea.
authors.forename: Youngseok
authors.initials: Y
authors.lastname: Lee
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D017952:Ganglia, Invertebrate / Q000378:metabolism*; D018628:Gene Dosage; D055879:Gene Knock-In Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels; D008715:Methionine / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; D005227:Fatty Acids; D051034:Inhibitor of Apoptosis Proteins; D007473:Ion Channels; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila; D008715:Methionine