Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila

Science. 1999 Sep 17;285(5435):1917-9. doi: 10.1126/science.285.5435.1917.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / metabolism*
  • Antimicrobial Cationic Peptides*
  • Body Patterning
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / immunology*
  • Drosophila Proteins*
  • Escherichia coli / genetics
  • Escherichia coli / immunology
  • Genes, Insect
  • Hemolymph / metabolism
  • Insect Proteins / biosynthesis*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Insect Proteins / physiology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Micrococcus luteus / immunology
  • Molecular Sequence Data
  • Mutagenesis
  • Peptides / genetics
  • Peptides / metabolism
  • Receptors, Cell Surface*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Serine Proteinase Inhibitors / genetics
  • Serine Proteinase Inhibitors / metabolism*
  • Serpins / genetics
  • Serpins / metabolism*
  • Signal Transduction
  • Toll-Like Receptors
  • Up-Regulation

Substances

  • Antifungal Agents
  • Antimicrobial Cationic Peptides
  • Drosophila Proteins
  • Insect Proteins
  • Membrane Glycoproteins
  • Peptides
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Serine Proteinase Inhibitors
  • Serpins
  • Tl protein, Drosophila
  • Toll-Like Receptors
  • spz protein, Drosophila
  • DRS protein, Drosophila
  • Mtk protein, Drosophila

Associated data

  • GENBANK/AJ245442
  • GENBANK/AJ245443
  • GENBANK/AJ245444