A single modular serine protease integrates signals from pattern-recognition receptors upstream of the Drosophila Toll pathway.
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.
Buchon
Nicolas
N
Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Poidevin
Mickael
M
Kwon
Hyun-Mi
HM
Guillou
Aurélien
A
Sottas
Valentin
V
Lee
Bok-Luel
BL
Lemaitre
Bruno
B
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D005658:Fungi / Q000502:physiology; D015870:Gene Expression; D006094:Gram-Positive Bacteria / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018411:Spodoptera; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D029721:Drosophila Proteins; C516487:GNBP3 protein, Drosophila; D047908:Intracellular Signaling Peptides and Proteins; D051192:Receptors, Pattern Recognition; D011993:Recombinant Fusion Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C118897:peptidoglycan recognition protein; D049452:Green Fluorescent Proteins; C543825:ModSP protein, Drosophila; D012697:Serine Endopeptidases