Persephone/Spätzle pathogen sensors mediate the activation of toll receptor signaling in response to endogenous danger signals in apoptosis-deficient Drosophila

Ming Ming, Fumiaki Obata, Erina Kuranaga, Masayuki Miura

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Apoptosis is an evolutionarily conserved mechanism that removes damaged or unwanted cells, effectively maintaining cellular homeostasis. It has long been suggested that a deficiency in this type of naturally occurring cell death could potentially lead to necrosis, resulting in the release of endogenous immunogenic molecules such as damage-associated molecular patterns (DAMPs) and a noninfectious inflammatory response. However, the details about how danger signals from apoptosis-deficient cells are detected and translated to an immune response are largely unknown. In this study, we found that Drosophila mutants deficient for Dronc, the key initiator caspase required for apoptosis, produced the active form of the endogenous Toll ligand Spätzle (Spz). We speculated that, as a system for sensing potential DAMPs in the hemolymph, the dronc mutants constitutively activate a proteolytic cascade that leads to Spz proteolytic processing. We demonstrated that Toll signaling activation required the action of Persephone, a CLIP domain serine protease that usually reacts to microbial proteolytic activities. Our findings show that the Persephone proteolytic cascade plays a crucial role in mediating DAMP-induced systemic responses in apoptosis-deficient Drosophila mutants.

Original languageEnglish
Pages (from-to)7558-7568
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number11
DOIs
Publication statusPublished - 2014 Mar 14
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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