title: Genetic Screen in Drosophila Larvae Links ird1 Function to Toll Signaling in the Fat Body and Hemocyte Motility.
abstract: To understand how Toll signaling controls the activation of a cellular immune response in Drosophila blood cells (hemocytes), we carried out a genetic modifier screen, looking for deletions that suppress or enhance the mobilization of sessile hemocytes by the gain-of-function mutation Toll10b (Tl10b). Here we describe the results from chromosome arm 3R, where five regions strongly suppressed this phenotype. We identified the specific genes immune response deficient 1 (ird1), headcase (hdc) and possibly Rab23 as suppressors, and we studied the role of ird1 in more detail. An ird1 null mutant and a mutant that truncates the N-terminal kinase domain of the encoded Ird1 protein affected the Tl10b phenotype, unlike mutations that affect the C-terminal part of the protein. The ird1 null mutant suppressed mobilization of sessile hemocytes, but enhanced other Tl10b hemocyte phenotypes, like the formation of melanotic nodules and the increased number of circulating hemocytes. ird1 mutants also had blood cell phenotypes on their own. They lacked crystal cells and showed aberrant formation of lamellocytes. ird1 mutant plasmatocytes had a reduced ability to spread on an artificial substrate by forming protrusions, which may explain why they did not go into circulation in response to Toll signaling. The effect of the ird1 mutation depended mainly on ird1 expression in hemocytes, but ird1-dependent effects in other tissues may contribute. Specifically, the Toll receptor was translocated from the cell membrane to intracellular vesicles in the fat body of the ird1 mutant, and Toll signaling was activated in that tissue, partially explaining the Tl10b-like phenotype. As ird1 is otherwise known to control vesicular transport, we conclude that the vesicular transport system may be of particular importance during an immune response.
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Schmid
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.|BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Ines
authors.initials: I
authors.lastname: Anderl
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.
authors.forename: Hoa T M
authors.initials: HT
authors.lastname: Vo
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Valanne
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.
authors.forename: Hairu
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kronhamn
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.|PEDEGO Research Center, and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Rämet
authors.affiliation: Department of Molecular Cell Biology, Oslo University Hospital, Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: Tor Erik
authors.initials: TE
authors.lastname: Rusten
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.|BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: Dan
authors.identifier: http://orcid.org/0000-0002-6506-5855
authors.initials: D
authors.lastname: Hultmark
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005216:Fat Body / Q000378:metabolism*; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism*; D007814:Larva / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins