title: Retromer promotes immune quiescence by suppressing Spätzle-Toll pathway in Drosophila.
abstract: The Toll and Toll-like receptor signaling pathways are evolutionarily conserved pathways that regulate innate immunity in insects and mammals. While efforts have been made to clarify the signal transduction events that occur during infection, much less is known about the components that maintain immune quiescence. Here we show that retromer, an intracellular protein complex known for regulating vesicle trafficking, functions in modulating the Toll pathway in Drosophila melanogaster. In mutant animals lacking retromer function, the Toll pathway but not JAK-STAT or IMD pathway is activated, triggering both cellular and humoral responses. Genetic epistasis and clonal analysis suggest that retromer regulates a component that acts upstream of Toll. Our data further show that in the mutant the Toll ligand Spätzle has a processing pattern similar to that of after infection. Together, the results suggest a novel function of retromer in regulating Toll pathway and innate immunity at a step that modulates ligand processing or activity.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and the Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.|Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon, 441-100, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Yun
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and the Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Ray
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and the Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
authors.forename: Y Tony
authors.initials: YT
authors.lastname: Ip
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and the Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.|State Key Laboratory of Biomembrane and Membrane Biotechnology, and Key Laboratory of Stem Cell, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D007113:Immunity, Innate; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D007814:Larva; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D050791:STAT Transcription Factors; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; C086179:spz protein, Drosophila; D053612:Janus Kinases; C085845:hop protein, Drosophila