Abstract
The Drosophila Toll receptor does not interact directly with microbial determinants, but is instead activated by a cleaved form of the cytokine-like molecule Spätzle. During the immune response, Spätzle is processed by complex cascades of serine proteases, which are activated by secreted pattern-recognition receptors. Here, we demonstrate the essential role of ModSP, a modular serine protease, in the activation of the Toll pathway by gram-positive bacteria and fungi. Our analysis shows that ModSP integrates signals originating from the circulating recognition molecules GNBP3 and PGRP-SA and connects them to the Grass-SPE-Spätzle extracellular pathway upstream of the Toll receptor. It also reveals the conserved role of modular serine proteases in the activation of insect immune reactions.
MeSH terms
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Amino Acid Sequence
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Line
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism
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Drosophila melanogaster / microbiology
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Fungi / physiology
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Gene Expression
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Gram-Positive Bacteria / physiology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Host-Pathogen Interactions
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Intracellular Signaling Peptides and Proteins
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Molecular Sequence Data
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Mutation
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Receptors, Pattern Recognition / genetics
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Receptors, Pattern Recognition / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism*
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Signal Transduction*
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Spodoptera
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Toll-Like Receptors / genetics
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Toll-Like Receptors / metabolism*
Substances
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Carrier Proteins
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Drosophila Proteins
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GNBP3 protein, Drosophila
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Intracellular Signaling Peptides and Proteins
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Receptors, Pattern Recognition
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Recombinant Fusion Proteins
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Tl protein, Drosophila
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Toll-Like Receptors
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peptidoglycan recognition protein
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Green Fluorescent Proteins
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ModSP protein, Drosophila
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Serine Endopeptidases