RRC ID 49537
Author Lee KA, Kim B, You H, Lee WJ.
Title Uracil-induced signaling pathways for DUOX-dependent gut immunity.
Journal Fly (Austin)
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.
Volume 9(3)
Pages 115-20
Published 2015-12-10
DOI 10.1080/19336934.2015.1126011
PMID 26655037
PMC PMC4862428
MeSH Animals Cadherins / metabolism Calcium / metabolism Disease Resistance Drosophila / genetics Drosophila / immunology* Drosophila / metabolism Enterocytes / drug effects Enterocytes / immunology Gene Expression Regulation Hedgehog Proteins / metabolism MAP Kinase Signaling System Membrane Microdomains / metabolism Membrane Microdomains / physiology Models, Immunological* NADPH Oxidases / metabolism NADPH Oxidases / physiology* Phospholipase C beta / metabolism Phospholipase C beta / physiology Signal Transduction Transcriptome / drug effects Uracil / pharmacology* Uracil / physiology
IF 1.204
Times Cited 6