The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation.
Eukaryotic peptidoglycan recognition proteins (PGRPs) are related to bacterial amidases. In Drosophila, PGRPs bind peptidoglycan and function as central sensors and regulators of the innate immune response. PGRP-LC/PGRP-LE constitute the receptor complex in the immune deficiency (IMD) pathway, which is an innate immune cascade triggered upon Gram-negative bacterial infection. Here, we present the functional analysis of the nonamidase, membrane-associated PGRP-LF. We show that PGRP-LF acts as a specific negative regulator of the IMD pathway. Reduction of PGRP-LF levels, in the absence of infection, is sufficient to trigger IMD pathway activation. Furthermore, normal development is impaired in the absence of functional PGRP-LF, a phenotype mediated by the JNK pathway. Thus, PGRP-LF prevents constitutive activation of both the JNK and the IMD pathways. We propose a model in which PGRP-LF keeps the Drosophila IMD pathway silent by sequestering circulating peptidoglycan.
Maillet
Frédéric
F
Institut de Biologie du Développement de Marseille-Luminy, UMR 6216 CNRS, Université de la Méditerannée Aix-Marseille II, Parc Scientifique de Luminy-Case 907, F-13288 Marseille Cedex 9, France.
Bischoff
Vincent
V
Vignal
Cécile
C
Hoffmann
Jules
J
Royet
Julien
J
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D006090:Gram-Negative Bacteria / Q000276:immunology; D007113:Immunity, Innate; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D015398:Signal Transduction
D002352:Carrier Proteins; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein; D048031:JNK Mitogen-Activated Protein Kinases