Deficiency of a blood serpin leads to constitutive activation of the toll-mediated antifungal defense in Drosophila

J.-M. Reichhart

UPR 9022 CNRS IBMC, 15, rue Rene Descartes, 67084 - Strasbourg Cedex, FRANCE

Mutants of the necrotic (nec) gene in Drosophila melanogaster die in the late pupal stage as pharate adults, or hatch as weak, but relatively normal-looking, flies. Adults develop black melanized spots on the body and leg joints, the abdomen swells with hemolymph and flies die within three or four days of eclosion. Pleiotropic nec phenotypes include melanization, necrosis and proliferation of epidermal cells. These changes are consistent with activation of one, or more, proteolytic cascades. The nec gene corresponds to Spn43Ac, one a cluster of three putative serine proteinase inhibitors (serpins) at 43A1.2, on the right arm of chromosome two. Although serpins have been implicated in the activation of many diverse pathways, lack of an individual serpin rarely causes a detectable phenotype. Molecular models of the three Spn43A serpins are presented. We show that a loss-of-function mutation in Spn43Ac, leads to constitutive expression of the antifungal peptide drosomycin and that the spaetzle and Toll gene products mediate this effect.. We argue that Spn43Ac negatively regulates the Toll signaling pathway and that Toll does not function in the Drosophila host defense as a pattern recognition receptor.

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