title: Drosophila immunity: a large-scale in vivo RNAi screen identifies five serine proteases required for Toll activation.
abstract: Unlike mammalian Toll-like Receptors, the Drosophila Toll receptor does not interact directly with microbial determinants but is rather activated upon binding a cleaved form of the cytokine-like molecule Spatzle (Spz). During the immune response, Spz is thought to be processed by secreted serine proteases (SPs) present in the hemolymph that are activated by the recognition of gram-positive bacteria or fungi . In the present study, we have used an in vivo RNAi strategy to inactivate 75 distinct Drosophila SP genes. We then screened this collection for SPs regulating the activation of the Toll pathway by gram-positive bacteria. Here, we report the identification of five novel SPs that function in an extracellular pathway linking the recognition proteins GNBP1 and PGRP-SA to Spz. Interestingly, four of these genes are also required for Toll activation by fungi, while one is specifically associated with signaling in response to gram-positive bacterial infections. These results demonstrate the existence of a common cascade of SPs upstream of Spz, integrating signals sent by various secreted recognition molecules via more specialized SPs.
authors.affiliation: Centre de Génétique Moléculaire, CNRS, Gif-sur-Yvette, France.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Kambris
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brun
authors.forename: In-Hwan
authors.initials: IH
authors.lastname: Jang
authors.forename: Hyuck-Jin
authors.initials: HJ
authors.lastname: Nam
authors.forename: Yves
authors.initials: Y
authors.lastname: Romeo
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Ryu
authors.initials: R
authors.lastname: Ueda
authors.forename: Bruno
authors.initials: B
authors.lastname: Lemaitre
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004330:Drosophila / Q000276:immunology*; D029721:Drosophila Proteins / Q000378:metabolism*; D013293:Enterococcus faecalis; D016908:Gram-Positive Bacterial Infections / Q000276:immunology; D016982:Micrococcus luteus; D034622:RNA Interference; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C118897:peptidoglycan recognition protein; C086179:spz protein, Drosophila; D012697:Serine Endopeptidases