The regulatory isoform rPGRP-LC induces immune resolution via endosomal degradation of receptors.
MetadataShow full item record
The innate immune system needs to distinguish between harmful and innocuous stimuli to adapt its activation to the level of threat. How Drosophila mounts differential immune responses to dead and live Gram-negative bacteria using the single peptidoglycan receptor PGRP-LC is unknown. Here we describe rPGRP-LC, an alternative splice variant of PGRP-LC that selectively dampens immune response activation in response to dead bacteria. rPGRP-LC-deficient flies cannot resolve immune activation after Gram-negative infection and die prematurely. The alternative exon in the encoding gene, here called rPGRP-LC, encodes an adaptor module that targets rPGRP-LC to membrane microdomains and interacts with the negative regulator Pirk and the ubiquitin ligase DIAP2. We find that rPGRP-LC-mediated resolution of an efficient immune response requires degradation of activating and regulatory receptors via endosomal ESCRT sorting. We propose that rPGRP-LC selectively responds to peptidoglycans from dead bacteria to tailor the immune response to the level of threat.
Version of record
Animals, Genetically Modified
Endosomal Sorting Complexes Required for Transport
Gene Knockout Techniques
Gram-Negative Bacterial Infections
Inhibitor of Apoptosis Proteins
Protein Sorting Signals
Cell Death and Inflammation
License start date
Nat Immunol, 17 (10), pp. 1150 - 1158
Showing items related by title, author, creator and subject.
Mardakheh, FK; Self, A; Marshall, CJDirectional cell migration involves reorientation of the secretory machinery. However, the molecular mechanisms that control this reorientation are not well characterised. Here, we identify a new Rho effector protein, named ...
Ecdysone-inducible expression of oncogenic Ha-Ras in NIH 3T3 cells leads to transient nuclear localization of activated extracellular signal-regulated kinase regulated by mitogen-activated protein kinase phosphatase-1. Plows, D; Briassouli, P; Owen, C; Zoumpourlis, V; Garrett, MD; Pintzas, A (2002-03)The Ras family of GTP-binding proteins are key transducers of extracellular signals, particularly through the mitogen-activated protein kinase (MAPK) pathway. Constitutively active forms of Ras are found in a variety of ...
International Cancer Genome Consortium PedBrain Tumor ProjectPediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously ...