Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila.
The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the spaetzle and Toll gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in Spn43Ac-deficient flies. Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense.
Levashina
E A
EA
UPR 9022 CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 Rue René Descartes, Strasbourg 67084, France.
Langley
E
E
Green
C
C
Gubb
D
D
Ashburner
M
M
Hoffmann
J A
JA
Reichhart
J M
JM
D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D019521:Body Patterning; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000276:immunology*; D029721:Drosophila Proteins; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D017344:Genes, Insect; D006458:Hemolymph / Q000378:metabolism; D019476:Insect Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D016982:Micrococcus luteus / Q000276:immunology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors; D015854:Up-Regulation
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C086179:spz protein, Drosophila; C091227:DRS protein, Drosophila; C096696:Mtk protein, Drosophila