Genomes and Genes
Gene Symbol: PGRP-LC
Description: Peptidoglycan recognition protein LC
Alias: (PGRP)-LC, CG4432, Dm PGRP-LC, Dmel\CG4432, PGRP-LCa, PGRP-LCx, PGRPLC, Pgrp-LC, ird7, pgrp lc, pgrp-lc, tot, peptidoglycan recognition protein LC, CG4432-PA, CG4432-PB, CG4432-PC, CG4432-PD, CG4432-PE, CG4432-PG, CG4432-PH, CG4432-PI, PGRP-LC-PA, PGRP-LC-PB, PGRP-LC-PC, PGRP-LC-PD, PGRP-LC-PE, PGRP-LC-PG, PGRP-LC-PH, PGRP-LC-PI, Peptidoglycan-recognition protein-LC, immune response deficient 7, peptidoglycan recognition protein-LC, totem
Species: fruit fly
- Bischoff V, Vignal C, Boneca I, Michel T, Hoffmann J, Royet J. Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol. 2004;5:1175-80 pubmed..These data indicate that PGRP-SD can function as a receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA-GNBP1 complex. ..
- Kleino A, Myllymäki H, Kallio J, Vanha aho L, Oksanen K, Ulvila J, et al. Pirk is a negative regulator of the Drosophila Imd pathway. J Immunol. 2008;180:5413-22 pubmed..pirk encodes a cytoplasmic protein that coimmunoprecipitates with Imd and the cytoplasmic tail of peptidoglycan recognition protein LC (PGRP-LC)...
- Zaidman Rémy A, Hervé M, Poidevin M, Pili Floury S, Kim M, Blanot D, et al. The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection. Immunity. 2006;24:463-73 pubmed..Our work highlights the key role of PGRPs that encode both sensors and scavengers of peptidoglycan, which modulate the level of the host immune response to the presence of infectious microorganisms. ..
- Choe K, Lee H, Anderson K. Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor. Proc Natl Acad Sci U S A. 2005;102:1122-6 pubmedDrosophila peptidoglycan recognition protein LC (PGRP-LC), a transmembrane protein required for the response to bacterial infection, acts at the top of a cytoplasmic signaling cascade that requires the death-domain protein Imd and an ..
- Tanji T, Hu X, Weber A, Ip Y. Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster. Mol Cell Biol. 2007;27:4578-88 pubmed..of antimicrobial peptide genes in Drosophila melanogaster is regulated by the conserved Toll and peptidoglycan recognition protein LC/immune deficiency (PGRP-LC/IMD) signaling pathways...
- Takehana A, Yano T, Mita S, Kotani A, Oshima Y, Kurata S. Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity. EMBO J. 2004;23:4690-700 pubmed..A role for PGRP-LE in the epithelial induction of antimicrobial peptides is also suggested. ..
- Pili Floury S, Leulier F, Takahashi K, Saigo K, Samain E, Ueda R, et al. In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults. J Biol Chem. 2004;279:12848-53 pubmed..Altogether, our results demonstrate that the detection of Gram-positive bacteria in Drosophila requires two putative pattern recognition receptors, PGRP-SA and GNBP1. ..
- Davis M, Primrose D, Hodgetts R. A member of the p38 mitogen-activated protein kinase family is responsible for transcriptional induction of Dopa decarboxylase in the epidermis of Drosophila melanogaster during the innate immune response. Mol Cell Biol. 2008;28:4883-95 pubmed publisher..We propose that the involvement of DDC in a new pathway involved in Drosophila immunity increases the levels of dopamine, which is metabolized to produce reactive quinones that exert an antimicrobial effect on invading bacteria. ..
- Buchon N, Broderick N, Chakrabarti S, Lemaitre B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 2009;23:2333-44 pubmed publisher..Altogether, these results indicate that gut homeostasis is achieved by a complex interregulation of the immune response, gut microbiota, and stem cell activity...
- Gottar M, Gobert V, Michel T, Belvin M, Duyk G, Hoffmann J, et al. The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature. 2002;416:640-4 pubmed..The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila. ..
- Ha E, Lee K, Park S, Kim S, Nam H, Lee H, et al. Regulation of DUOX by the Galphaq-phospholipase Cbeta-Ca2+ pathway in Drosophila gut immunity. Dev Cell. 2009;16:386-97 pubmed publisher..These results demonstrate that the Galphaq-PLCbeta-Ca(2+)-DUOX-ROS signaling pathway acts as a bona fide first line of defense that enables gut epithelia to dynamically control yeast during the Drosophila life cycle. ..
- Paquette N, Broemer M, Aggarwal K, Chen L, Husson M, Erturk Hasdemir D, et al. Caspase-mediated cleavage, IAP binding, and ubiquitination: linking three mechanisms crucial for Drosophila NF-kappaB signaling. Mol Cell. 2010;37:172-82 pubmed publisher..Through its association with DIAP2, IMD is rapidly conjugated with K63-linked polyubiquitin chains. These results mechanistically connect caspase-mediated cleavage and K63 ubiquitination in immune-induced NF-kappaB signaling. ..
- Ha E, Lee K, Seo Y, Kim S, Lim J, Oh B, et al. Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in drosophila gut. Nat Immunol. 2009;10:949-57 pubmed publisher..Thus, the coordinated regulation of DUOX enables the host to achieve gut-microbe homeostasis by efficiently combating infection while tolerating commensal microbes. ..
- Thevenon D, Engel E, Avet Rochex A, Gottar M, Bergeret E, Tricoire H, et al. The Drosophila ubiquitin-specific protease dUSP36/Scny targets IMD to prevent constitutive immune signaling. Cell Host Microbe. 2009;6:309-20 pubmed publisher..Our findings identify dUSP36 as a repressor whose IMD deubiquitination activity prevents nonspecific activation of innate immune signaling. ..
- Garver L, Wu J, Wu L. The peptidoglycan recognition protein PGRP-SC1a is essential for Toll signaling and phagocytosis of Staphylococcus aureus in Drosophila. Proc Natl Acad Sci U S A. 2006;103:660-5 pubmed
- DiAngelo J, Bland M, Bambina S, Cherry S, Birnbaum M. The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proc Natl Acad Sci U S A. 2009;106:20853-8 pubmed publisher..These data suggest that communication between these two regulatory systems evolved as a means to divert energy in times of need from organismal growth to the acute requirement of combating infection...
- Hoffmann J. The immune response of Drosophila. Nature. 2003;426:33-8 pubmed..Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity. ..
- Rus F, Flatt T, Tong M, Aggarwal K, Okuda K, Kleino A, et al. Ecdysone triggered PGRP-LC expression controls Drosophila innate immunity. EMBO J. 2013;32:1626-38 pubmed publisher..Together, our results demonstrate that Drosophila use complex mechanisms to modulate innate immune responses, and identify a transcriptional hierarchy that integrates steroid signalling and immunity in animals. ..
- Ha E, Oh C, Ryu J, Bae Y, Kang S, Jang I, et al. An antioxidant system required for host protection against gut infection in Drosophila. Dev Cell. 2005;8:125-32 pubmed..These results imply that homeostasis of redox balance by IRC is one of the most critical factors affecting host survival during continuous host-microbe interaction in the gastrointestinal tract. ..
- Meinander A, Runchel C, Tenev T, Chen L, Kim C, Ribeiro P, et al. Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling. EMBO J. 2012;31:2770-83 pubmed publisher..The direct involvement of ubiquitylation in caspase activation represents a novel mechanism for non-apoptotic caspase-mediated signalling. ..
- Wagner C, Isermann K, Fehrenbach H, Roeder T. Molecular architecture of the fruit fly's airway epithelial immune system. BMC Genomics. 2008;9:446 pubmed publisher..This architecture will allow reacting if confronted with different bacterial or fungal elicitors by activation of a multitude of effectors. ..
- Choe K, Werner T, Stoven S, Hultmark D, Anderson K. Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science. 2002;296:359-62 pubmed
- Maillet F, Bischoff V, Vignal C, Hoffmann J, Royet J. The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation. Cell Host Microbe. 2008;3:293-303 pubmed publisher..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. ..
- Bosco Drayon V, Poidevin M, Boneca I, Narbonne Reveau K, Royet J, Charroux B. Peptidoglycan sensing by the receptor PGRP-LE in the Drosophila gut induces immune responses to infectious bacteria and tolerance to microbiota. Cell Host Microbe. 2012;12:153-65 pubmed publisher..Together these data indicate that PGRP-LE functions as a master gut bacterial sensor that induces balanced responses to infectious bacteria and tolerance to microbiota. ..
- Werner T, Liu G, Kang D, Ekengren S, Steiner H, Hultmark D. A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster. Proc Natl Acad Sci U S A. 2000;97:13772-7 pubmed..We demonstrate that at least PGRP-SA and SC1B can bind peptidoglycan, and a function in immunity is likely for this family. ..
- Kaneko T, Goldman W, Mellroth P, Steiner H, Fukase K, Kusumoto S, et al. Monomeric and polymeric gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway. Immunity. 2004;20:637-49 pubmed..Recognition of monomeric and polymeric peptidoglycan required different PGRP-LC splice isoforms, while lipid A recognition required an unidentified soluble factor in the hemolymph of Bombyx morii. ..
- Bischoff V, Vignal C, Duvic B, Boneca I, Hoffmann J, Royet J. Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2. PLoS Pathog. 2006;2:e14 pubmed..We further show that a strict control of IMD-pathway activation is essential to prevent bacteria-induced developmental defects and larval death. ..
- Leulier F, Parquet C, Pili Floury S, Ryu J, Caroff M, Lee W, et al. The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat Immunol. 2003;4:478-84 pubmed..Thus, the ability of Drosophila to discriminate between Gram-positive and Gram-negative bacteria relies on the recognition of specific forms of peptidoglycan. ..
- Werner T, Borge Renberg K, Mellroth P, Steiner H, Hultmark D. Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan. J Biol Chem. 2003;278:26319-22 pubmed..Two additional PGRP domains in the gene cluster, z and w, are both included in a single transcript of a separate gene, PGRP-LF. Suppression of this transcript does not block the response to any of the microorganisms tested. ..
- Kim M, Lee J, Lee S, Kim E, Chung J. Caspar, a suppressor of antibacterial immunity in Drosophila. Proc Natl Acad Sci U S A. 2006;103:16358-63 pubmed..Collectively, our elucidation of an inhibitory mechanism of the Imd pathway by Caspar will provide a valuable insight into understanding complex regulatory mechanisms of the innate immune systems in both Drosophila and mammals. ..
- Erturk Hasdemir D, Broemer M, Leulier F, Lane W, Paquette N, Hwang D, et al. Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes. Proc Natl Acad Sci U S A. 2009;106:9779-84 pubmed publisher..Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish. ..
- Tsichritzis T, Gaentzsch P, Kosmidis S, Brown A, SKOULAKIS E, Ligoxygakis P, et al. A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense. Development. 2007;134:2605-14 pubmed..All mutant phenotypes described were reversible upon conditional expression of CYLD transgenes. Our results implicate CYLD in a broad range of functions associated with fat homeostasis and host defence in Drosophila. ..
- Yano T, Mita S, Ohmori H, Oshima Y, Fujimoto Y, Ueda R, et al. Autophagic control of listeria through intracellular innate immune recognition in drosophila. Nat Immunol. 2008;9:908-16 pubmed publisher..Autophagy induction occurred independently of the Toll and IMD innate signaling pathways. Our findings define a pathway leading from the intracellular pattern-recognition receptors to the induction of autophagy to host defense...
- Linder J, Owers K, Promislow D. The effects of temperature on host-pathogen interactions in D. melanogaster: who benefits?. J Insect Physiol. 2008;54:297-308 pubmed..The approach described here allows us to determine whether this effect is due primarily to temperature-specific effects on the host or on its pathogen. These results suggest that both may be important. ..
- Erturk Hasdemir D, Silverman N. Eater: a big bite into phagocytosis. Cell. 2005;123:190-2 pubmed..In this issue of Cell, Kocks et al. (2005) demonstrate that Eater, a scavenger receptor, plays an important role in the recognition and phagocytosis of bacteria in the fruit fly Drosophila. ..
- Chakrabarti S, Poidevin M, Lemaitre B. The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine. PLoS Genet. 2014;10:e1004659 pubmed publisher..Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila. It also reveals that many roles initially attributed to p38a are in fact mediated by p38c. ..
- Douglas A, Bouvaine S, Russell R. How the insect immune system interacts with an obligate symbiotic bacterium. Proc Biol Sci. 2011;278:333-8 pubmed publisher..They support the proposed contribution of the Buchnera symbiosis to the evolution of the apparently reduced immune function in the aphid host. ..
- Clark R, Salazar A, Yamada R, Fitz Gibbon S, Morselli M, Alcaraz J, et al. Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality. Cell Rep. 2015;12:1656-67 pubmed publisher..Our results indicate that alterations in microbiota dynamics could contribute to and also predict varying rates of health decline during aging in mammals. ..
- Swaminathan C, Brown P, Roychowdhury A, Wang Q, Guan R, Silverman N, et al. Dual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs). Proc Natl Acad Sci U S A. 2006;103:684-9 pubmed..The plasticity of the PGRP-binding site revealed by these mutants suggests an intrinsic capacity of the innate immune system to rapidly evolve specificities to meet new microbial challenges. ..
- Vanha aho L, Kleino A, Kaustio M, Ulvila J, Wilke B, Hultmark D, et al. Functional characterization of the infection-inducible peptide Edin in Drosophila melanogaster. PLoS ONE. 2012;7:e37153 pubmed publisher..faecalis infection via an uncharacterized mechanism. Further studies are still required to elucidate the exact role of Edin in the Drosophila immune response. ..
- Kwiatkowski D. The complexity of genetic variation in a simple immune system. Trends Genet. 2005;21:197-9 pubmed..However, the effects of individual polymorphisms on the resistance phenotype were modest, and epistatic interactions appeared to be common. What might these findings tell us about genetic resistance to infection in humans? ..
- Goto A, Fukuyama H, Imler J, Hoffmann J. The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response. J Biol Chem. 2014;289:20470-6 pubmed..Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling. ..
- Leone P, Bischoff V, Kellenberger C, Hetru C, Royet J, Roussel A. Crystal structure of Drosophila PGRP-SD suggests binding to DAP-type but not lysine-type peptidoglycan. Mol Immunol. 2008;45:2521-30 pubmed publisher..Our hypothesis is that the role of PGRP-SD is the recognition of DAP-type PGNs responsible for the activation of the Toll pathway by Gram-negative bacteria. ..
- Horiguchi T, Fuka M, Fujisawa K, Tanimura A, Miyoshi K, Murakami R, et al. Adenylate kinase 2 deficiency limits survival and regulates various genes during larval stages of Drosophila melanogaster. J Med Invest. 2014;61:137-50 pubmed..These data indicate that adenine nucleotide interconversion by Dak2 is crucial for developmental processes of Drosophila melanogaster. ..
- Ji S, Sun M, Zheng X, Li L, Sun L, Chen D, et al. Cell-surface localization of Pellino antagonizes Toll-mediated innate immune signalling by controlling MyD88 turnover in Drosophila. Nat Commun. 2014;5:3458 pubmed publisher..Collectively, our study uncovers a mechanism by which a feedback regulatory loop involving MyD88 and Pellino controls Toll-mediated signalling, thereby maintaining homeostasis of host innate immunity. ..
- Donlea J, Ramanan N, Silverman N, Shaw P. Genetic rescue of functional senescence in synaptic and behavioral plasticity. Sleep. 2014;37:1427-37 pubmed publisher..These studies demonstrate that Drosophila provides a promising model for the study of age-related loss of neural plasticity and begin to identify genes that might be manipulated to delay the onset of functional senescence. ..
- Goto A, Yano T, Terashima J, Iwashita S, Oshima Y, Kurata S. Cooperative regulation of the induction of the novel antibacterial Listericin by peptidoglycan recognition protein LE and the JAK-STAT pathway. J Biol Chem. 2010;285:15731-8 pubmed publisher..Based on these findings, we propose that the Listericin gene encodes a novel antibacterial peptide-like protein whose induction is cooperatively regulated by PGRP-LE and the JAK-STAT pathway. ..
- Sackton T, Lazzaro B, Clark A. Genotype and gene expression associations with immune function in Drosophila. PLoS Genet. 2010;6:e1000797 pubmed publisher..These results show that polymorphism in genes near the top of the immune system signaling cascade can have a disproportionate effect on organismal phenotype due to the amplification of minor effects through the cascade. ..
- McGettigan J, McLennan R, Broderick K, Kean L, Allan A, Cabrero P, et al. Insect renal tubules constitute a cell-autonomous immune system that protects the organism against bacterial infection. Insect Biochem Mol Biol. 2005;35:741-54 pubmed..coli challenge. Thus, we describe a novel role of Malpighian tubules in immune sensing and insect survival. ..
- Goto A, Matsushita K, Gesellchen V, El Chamy L, Kuttenkeuler D, Takeuchi O, et al. Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice. Nat Immunol. 2008;9:97-104 pubmed..Thus, Akirin is a conserved nuclear factor required for innate immune responses. ..
- Neyen C, Runchel C, Schüpfer F, Meier P, Lemaitre B. The regulatory isoform rPGRP-LC induces immune resolution via endosomal degradation of receptors. Nat Immunol. 2016;17:1150-8 pubmed publisher..We propose that rPGRP-LC selectively responds to peptidoglycans from dead bacteria to tailor the immune response to the level of threat. ..
- Lee J, Edery I. Circadian regulation in the ability of Drosophila to combat pathogenic infections. Curr Biol. 2008;18:195-9 pubmed publisher..Our findings suggest that medical intervention strategies incorporating chronobiological considerations could enhance the innate immune response, boosting the efficacy of combating pathogenic infections. ..
- Nelson B, Freisinger T, Ishii K, Okado K, Shinzawa N, Fukumoto S, et al. Activation of Imd pathway in hemocyte confers infection resistance through humoral response in Drosophila. Biochem Biophys Res Commun. 2013;430:1120-5 pubmed publisher..aureus, counter to notions of traditional roles of the Imd pathway thought largely to responsible for resistance to Gram-negative bacteria. ..
- Aparicio R, Neyen C, Lemaitre B, Busturia A. dRYBP contributes to the negative regulation of the Drosophila Imd pathway. PLoS ONE. 2013;8:e62052 pubmed publisher..Beyond the identification of dRYBP as a novel component of Imd pathway regulation, our results also suggest that the evolutionarily conserved RYBP protein may be involved in the human innate immune response. ..
- Khush R, Leulier F, Lemaitre B. Immunology. Pathogen surveillance--the flies have it. Science. 2002;296:273-5 pubmed
- Vandenabeele P, Bertrand M. The role of the IAP E3 ubiquitin ligases in regulating pattern-recognition receptor signalling. Nat Rev Immunol. 2012;12:833-44 pubmed publisher..Understanding the role of IAPs in innate immunity may open new therapeutic perspectives for the treatment of PRR-dependent inflammatory diseases. ..
- Tsuzuki S, Ochiai M, Matsumoto H, Kurata S, Ohnishi A, Hayakawa Y. Drosophila growth-blocking peptide-like factor mediates acute immune reactions during infectious and non-infectious stress. Sci Rep. 2012;2:210 pubmed publisher..These results indicate that the Drosophila GBP signaling pathway mediates acute innate immune reactions under various stresses, regardless of whether they are infectious or non-infectious. ..
- Aymeric J, Givaudan A, Duvic B. Imd pathway is involved in the interaction of Drosophila melanogaster with the entomopathogenic bacteria, Xenorhabdus nematophila and Photorhabdus luminescens. Mol Immunol. 2010;47:2342-8 pubmed publisher..coli-induced protection. However, phoP recovered a level of pathogenicity comparable to P. luminescens wild-type TT01 when injected to Drosophila flies affected on the imd pathway. ..
- You H, Lee W, Lee W. Homeostasis between gut-associated microorganisms and the immune system in Drosophila. Curr Opin Immunol. 2014;30:48-53 pubmed publisher..A deeper understanding of the role of uracil in Drosophila immunity will provide additional insight into the molecular mechanisms underlying host-microbe symbiosis and dysbiosis. ..