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

TitleImmune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic.
Publication TypeJournal Article
Year of Publication2006
AuthorsPelte N, Robertson AS, Zou Z, Belorgey D, Dafforn TR, Jiang H, Lomas D, Reichhart J-M, Gubb D
JournalInsect biochemistry and molecular biology
Volume36
Issue1
Pagination37-46
Date Published2006 Jan
ISSN0965-1748
KeywordsAnimals, Drosophila melanogaster, Drosophila Proteins, Gene Expression Regulation, Protein Conformation, Serpins, Signal Transduction
Abstract

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, SpƤtzle. 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.

DOI10.1016/j.ibmb.2005.10.004
Alternate JournalInsect Biochem. Mol. Biol.


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