title: Uracil-induced signaling pathways for DUOX-dependent gut immunity.
abstract: Intestinal dual oxidase (DUOX) activation is the first line of host defense against enteric infection in Drosophila. DUOX enzymatic activity is mainly controlled by phospholipase C-β (PLCβ)-dependent calcium mobilization, whereas DUOX gene expression is mainly controlled by the MEKK1-p38 mitogen-activated protein kinase pathway. Furthermore, bacterial-derived uracil molecules act as ligands for DUOX activation. However, our current understanding of uracil-induced signal transduction pathways remain incomplete. We have recently found that uracil stimulates Hedgehog signaling, which in turn upregulates cadherin99C (Cad99C) expression in enterocytes. Cad99C molecules, along with PLCβ and protein kinase C, induce the formation of signaling endosomes that facilitate intracellular calcium mobilization for DUOX activity. These observations illustrate the complexity of signaling cascades in uracil-induced signaling pathways. Here, we further demonstrated the role of lipid raft formation and calmodulin-dependent protein kinase-II on endosome formation and calcium mobilization, respectively. Moreover, we will provide a brief discussion on two different models for uracil recognition and uracil-induced DUOX activation in Drosophila enterocytes.
authors.affiliation: a School of Biological Science, Seoul National University and National Creative Research Initiative Center for Hologenomics, Seoul National University , Seoul , South Korea.|b Institute of Molecular Biology and Genetics, Seoul National University , Seoul , South Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Lee
authors.affiliation: a School of Biological Science, Seoul National University and National Creative Research Initiative Center for Hologenomics, Seoul National University , Seoul , South Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Kim
authors.affiliation: a School of Biological Science, Seoul National University and National Creative Research Initiative Center for Hologenomics, Seoul National University , Seoul , South Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: You
authors.affiliation: a School of Biological Science, Seoul National University and National Creative Research Initiative Center for Hologenomics, Seoul National University , Seoul , South Korea.|b Institute of Molecular Biology and Genetics, Seoul National University , Seoul , South Korea.
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D060467:Disease Resistance; D004330:Drosophila / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020895:Enterocytes / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D021962:Membrane Microdomains / Q000378:metabolism / Q000502:physiology; D018448:Models, Immunological; D019255:NADPH Oxidases / Q000378:metabolism / Q000502:physiology*; D054799:Phospholipase C beta / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D059467:Transcriptome / Q000187:drug effects; D014498:Uracil / Q000494:pharmacology* / Q000502:physiology
chemical_list: C512040:Cad99c protein, Drosophila; D015820:Cadherins; D053823:Hedgehog Proteins; C505384:dual oxidase, Drosophila; D014498:Uracil; D019255:NADPH Oxidases; D054799:Phospholipase C beta; D002118:Calcium
keywords: Calmodulin-dependent kinase II; Drosophila; Uracil; dual oxidase; gut immunity; hedgehog signaling; lipid raft; reactive oxygen species