title: The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Maillet
authors.forename: Vincent
authors.initials: V
authors.lastname: Bischoff
authors.forename: Cécile
authors.initials: C
authors.lastname: Vignal
authors.forename: Jules
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Julien
authors.initials: J
authors.lastname: Royet
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein; D048031:JNK Mitogen-Activated Protein Kinases