More Than Black or White: Melanization and Toll Share Regulatory Serine Proteases in Drosophila

Cell Rep. 2019 Apr 23;27(4):1050-1061.e3. doi: 10.1016/j.celrep.2019.03.101.

Abstract

The melanization response is an important defense mechanism in arthropods. This reaction is mediated by phenoloxidases (POs), which are activated by complex extracellular serine protease (SP) cascades. Here, we investigate the role of SPs in the melanization response using compound mutants in D. melanogaster and discover phenotypes previously concealed in single-mutant analyses. We find that two SPs, Hayan and Sp7, activate the melanization response in different manners: Hayan is required for blackening wound sites, whereas Sp7 regulates an alternate melanization reaction responsible for the clearance of Staphylococcus aureus. We present evidence that Sp7 is regulated by SPs activating the Toll NF-κB pathway, namely ModSP and Grass. Additionally, we reveal a role for the combined action of Hayan and Psh in propagating Toll signaling downstream of pattern recognition receptors activating either Toll signaling or the melanization response.

Keywords: Drosophila; Toll pathway; gene duplication; immunity; melanization; prophenoloxidase; serine protease.

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / microbiology
  • Gene Duplication
  • Host-Pathogen Interactions
  • Melanins / metabolism*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Serine Endopeptidases / physiology
  • Serine Proteases / genetics
  • Serine Proteases / metabolism
  • Serine Proteases / physiology*
  • Staphylococcus aureus / physiology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Toll-Like Receptors / physiology

Substances

  • Drosophila Proteins
  • Melanins
  • Tl protein, Drosophila
  • Toll-Like Receptors
  • Serine Proteases
  • Serine Endopeptidases
  • Sp7 protein, Drosophila
  • psh protein, Drosophila