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Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes

Title
 Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes
Authors
 Kyung-Ah Lee; Boram Kim; Won-Jae Lee; Daehee Hwang; Ji-Hwan Ryu; Sung-Hee Kim; Eun-Kyoung Kim; Hyejin You; Do Hun Kim; Jinhyuk Bhin
Issue Date
2015
Journal Title
 Cell Host & Microbe
ISSN
 1931-3128
Citation
 Cell Host & Microbe, Vol.17(2) : 191~204, 2015
Abstract
Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLCβ/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of Cad99C into enterocytes, demonstrating the important role for Hh signaling in host resistance to enteric infection.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/140703
DOI
10.1016/j.chom.2014.12.012
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Research Center for Human Natural Defense System
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S1931312814004661
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