Genetic Screen in Drosophila Larvae Links ird1 Function to Toll Signaling in the Fat Body and Hemocyte Motility

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Genetic Screen in Drosophila Larvae Links ird1 Function to Toll Signaling in the Fat Body and Hemocyte Motility

Schmid, Martin R. (author): Uppsala universitet,Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Institutionen för medicinsk biokemi och mikrobiologi,Umea Univ, Dept Mol Biol, Umea, Sweden.

Anderl, Ines (author): Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),BioMediTech, University of Tampere, Tampere, Finland,Umea Univ, Dept Mol Biol, Umea, Sweden.;Univ Tampere, BioMediTech, Tampere, Finland.

Vo, Hoa T. M. (author): Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Umea Univ, Dept Mol Biol, Umea, Sweden.

Valanne, Susanna (author): Univ Tampere, BioMediTech, Tampere, Finland.

Yang, Hairu (author): Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Umea Univ, Dept Mol Biol, Umea, Sweden.

Kronhamn, Jesper (author): Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Umea Univ, Dept Mol Biol, Umea, Sweden.

Ramet, Mika (author): Univ Tampere, BioMediTech, Tampere, Finland.;Univ Oulu, PEDEGO Res Ctr, Oulu, Finland.;Univ Oulu, Med Res Ctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Oulu, Finland.

Rusten, Tor Erik (author): Univ Oslo, Ctr Canc Biomed, Oslo Univ Hosp, Dept Mol Cell Biol, Oslo, Norway.

Hultmark, Dan (author): Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),BioMediTech, University of Tampere, Tampere, Finland,Umea Univ, Dept Mol Biol, Umea, Sweden.;Univ Tampere, BioMediTech, Tampere, Finland.

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2016-07-28
2016
English.
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7

Related links:: https://doi.org/10.1...; show more...; https://umu.diva-por... (primary) (Raw object); https://journals.plo...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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 Toll(10b) (Tl-10b). 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 Tl-10b phenotype, unlike mutations that affect the C-terminal part of the protein. The ird1 null mutant suppressed mobilization of sessile hemocytes, but enhanced other Tl-10b 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 Tl-10b-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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)

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By the author/editor: Schmid, Martin R ...; Anderl, Ines; Vo, Hoa T. M.; Valanne, Susanna; Yang, Hairu; Kronhamn, Jesper; show more...; Ramet, Mika; Rusten, Tor Erik; Hultmark, Dan; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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By the university: Umeå University; Uppsala University

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