A single modular serine protease integrates signals from pattern-recognition receptors upstream of the Drosophila Toll pathway

Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12442-7. doi: 10.1073/pnas.0901924106. Epub 2009 Jul 9.

Abstract

The Drosophila Toll receptor does not interact directly with microbial determinants, but is instead activated by a cleaved form of the cytokine-like molecule Spätzle. During the immune response, Spätzle is processed by complex cascades of serine proteases, which are activated by secreted pattern-recognition receptors. Here, we demonstrate the essential role of ModSP, a modular serine protease, in the activation of the Toll pathway by gram-positive bacteria and fungi. Our analysis shows that ModSP integrates signals originating from the circulating recognition molecules GNBP3 and PGRP-SA and connects them to the Grass-SPE-Spätzle extracellular pathway upstream of the Toll receptor. It also reveals the conserved role of modular serine proteases in the activation of insect immune reactions.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / microbiology
  • Fungi / physiology
  • Gene Expression
  • Gram-Positive Bacteria / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Host-Pathogen Interactions
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Mutation
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction*
  • Spodoptera
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*

Substances

  • Carrier Proteins
  • Drosophila Proteins
  • GNBP3 protein, Drosophila
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Pattern Recognition
  • Recombinant Fusion Proteins
  • Tl protein, Drosophila
  • Toll-Like Receptors
  • peptidoglycan recognition protein
  • Green Fluorescent Proteins
  • ModSP protein, Drosophila
  • Serine Endopeptidases