Immune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic

N Pelte, AS Robertson, Z Zou, D Berlorgey, Timothy Dafforn, HB Jiang, D Lomas, JM Reichhart, D Gubb

Research output: Contribution to journalArticle

23 Citations (Scopus)


The Drosophila Necrotic protein is a serine proteinase inhibitor, which regulates the Toll-mediated innate immune response. Necrotic specifically inhibits an extracellular serine proteinase cascade leading to activation of the Toll ligand, Spätzle. Necrotic carries a polyglutamine extension amino-terminal to the core serpin structure. We show here that cleavage of this N-terminal extension occurs following immune challenge. This modification is blocked in PGRP-SA(semmelweiss) mutants after Gram-positive bacterial challenge and in persephone mutants after fungal or Gram-positive bacterial challenge, indicating that activation of either of the Toll pathway upstream branches induces N-terminal cleavage of the serpin. The absolute requirement of persephone gene product for this cleavage indicates that Gram-positive bacteria activate a redundant set of proteinases upstream of Toll. Both full-length Necrotic and the core serpin are active inhibitors of a range of serine proteinases: the highest affinity being for cathepsin G and elastases. We found a 13-fold increase in the specificity of the core serpin over that of full-length Necrotic for one of the tested proteinases (porcine pancreatic elastase). This finding indicates that cleavage of the Necrotic amino-terminal extension might modulate Toll activation following the initial immune response.
Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalInsect Biochemistry and Molecular Biology
Issue number1
Publication statusPublished - 1 Jan 2006


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