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bioRxiv · 10.1101/383257

More than black and white: complex relationships involving serine proteases regulate the Toll pathway and the melanization response in Drosophila

Dudzic, J. P.·Hanson, M. A.·Iatsenko, I.·Kondo, S.·Lemaitre, B.
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Abstract

The melanization response is a rapid and important defense mechanism in arthropods. Melanin is produced around wound sites and invading microorganisms by phenoloxidases (POs), which need to be activated by the sequential activation of an extracellular serine protease (SP) cascade. Drosophila melanogaster has been a useful genetic model for dissecting insect immune signaling, but understanding these proteolytic cascades has been complicated by the large number of SP genes, possibly with redundant function. Taking advantage of recently-generated null and compound mutants, we re-investigated the role of SPs involved in the melanization response in D. melanogaster and discovered phenotypes previously concealed in single mutant analysis. We found that two of them, Hayan and Sp7, can activate the melanization response in two different manners: Hayan is required in the local blackening of wound sites, while Sp7 regulates an alternate melanization reaction responsible for the clearance of septic infections with Staphylococcus aureus. We present evidence that both Sp7 and Hayan regulate the Toll NF-kB pathway. Sp7 is regulated by canonical Toll signaling downstream of PGRP-SA, ModSP, and Grass, leading to control of septic infections via a Sp7-dependent melanization response. Additionally, we found that Hayan and the Toll-regulating SP Psh are the result of a recent gene duplication. Using genetic manipulations, we reveal the hidden role for Hayan, alongside Psh, in propagating Toll signaling downstream of pattern recognition receptors. Thus, we describe the existence of two pathways leading to the melanization response and reveal previously unknown dynamics in the activation of the Toll pathway.

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Dudzic, J. P., Hanson, M. A., Iatsenko, I., Kondo, S., Lemaitre, B.. 2018-08-02. More than black and white: complex relationships involving serine proteases regulate the Toll pathway and the melanization response in Drosophila. https://doi.org/10.1101/383257

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