A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans

Pujol, Nathalie; Link, Elizabeth Malone; Liu, Leo X.; Kurz, C. Léopold; Alloing, Geneviève; Tan, Man‐Wah; Ray, Keith P.; Solari, Roberto; Johnson, Carl D.; Ewbank, Jonathan J.

doi:10.1016/s0960-9822(01)00241-x

Cited by 377 publications

(209 citation statements)

References 71 publications

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“…Worms are attracted to, or avoid, different bacteria [68,105,106], and it is not yet known whether these behaviors are mediated primarily via a single bacterially produced chemical, or whether a set of chemicals must be recognized as an ensemble to provide a chemical signature for a specific bacterial strain. Similarly, although a major regulator of worm behavior and development is levels of the constitutively produced dauer pheromone [8][9][10][107][108][109], the neurons that respond to pheromone are also not yet defined.…”

Section: Mapping Chemicals To Chemosensory Neuronsmentioning

confidence: 99%

Generation and modulation of chemosensory behaviors in C. elegans

Sengupta

2007

Pflugers Arch - Eur J Physiol

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C. elegans recognizes and discriminates among hundreds of chemical cues using a relatively compact chemosensory nervous system. Chemosensory behaviors are also modulated by prior experience and contextual cues. Because of the facile genetics and genomics possible in this organism, C. elegans provides an excellent system in which to explore the generation of chemosensory behaviors from the level of a single gene to the motor output. This review summarizes the current knowledge on the molecular and neuronal substrates of chemosensory behaviors and chemosensory behavioral plasticity in C. elegans.

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Section: Mapping Chemicals To Chemosensory Neuronsmentioning

confidence: 99%

Generation and modulation of chemosensory behaviors in C. elegans

Sengupta

2007

Pflugers Arch - Eur J Physiol

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“…In contrast, relatively little is known about innate immunity in the nematode Caenorhabditis elegans. Recent work has shown that C. elegans is killed by a variety of bacterial and fungal pathogens, including Pseudomonas aeruginosa (4)(5)(6)(7)(8)(9)(10)(11)(12). When this experimental host-pathogen system was used, a forward genetic screen for C. elegans mutants exhibiting enhanced susceptibility to P. aeruginosa-mediated killing (Esp phenotype) identified two components of a mitogen-activated protein kinase (MAPK) signaling cascade, the MAPK kinase kinase, NSY-1, and the MAPK kinase, SEK-1, that are required for pathogen resistance (13).…”

mentioning

confidence: 99%

Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response

Liberati

Fitzgerald

Kim

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

213

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The p38 mitogen-activated protein kinase pathway regulates innate immune responses in evolutionarily diverse species. We have previously shown that the Caenorhabditis elegans p38 mitogenactivated protein kinase, PMK-1, functions in an innate immune response pathway that mediates resistance to a variety of microbial pathogens. Here, we show that tir-1, a gene encoding a highly conserved Toll͞IL-1 resistance (TIR) domain protein, is also required for C. elegans resistance to microbial pathogens. RNA interference inactivation of tir-1 resulted in enhanced susceptibility to killing by pathogens and correspondingly diminished PMK-1 phosphorylation. Unlike all known TIR-domain adapter proteins, overexpression of the human TIR-1 homologue, SARM, in mammalian cells was not sufficient to induce expression of NF-B or IRF3-dependent reporter genes that are activated by Toll-like receptor signaling. These data reveal the involvement of a previously uncharacterized, evolutionarily conserved TIR domain protein in innate immunity that is functionally distinct from other known TIR domain signaling adapters.

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“…These important and diverse functions make NF-B one of the best-studied transcriptional factors in biology (2). Unexpectedly, in Caenorhabditis elegans, the NF-B protein is absent, and similar functional homologues (Toll, Traf, Cactus) are not involved in innate immune response (5). This led to the suggestion that the p38 mitogen-activated protein kinase pathway, which mediates the immune response in C. elegans, is the ancestral signaling pathway of the common ancestor of nematodes, arthropods, and vertebrates, predating the evolution of the NF-B immune signaling pathway (6).…”

mentioning

confidence: 99%

Evidence for the ancient origin of the NF-κB/IκB cascade: Its archaic role in pathogen infection and immunity

Wang

Tan²,

Ho³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The evolutionary conservation of the NF-B transcription factors, from Drosophila to humans, underscores its pivotal role in immune response. Unexpectedly, the canonical NF-B signaling pathway is not functional in the immune system of Caenorhabditis elegans. Therefore, the ancient origin of the NF-B signaling pathway is still unknown. Here, we report the discovery and characterization of a primitive and functional NF-B͞I B pathway in the immune defense of a ''living fossil,'' the horseshoe crab, Carcinoscorpius rotundicauda. The ancient NF-B͞I B homologues, CrNF B, CrRelish, and CrI B, share numerous signature motifs with their vertebrate orthologues. CrNF B recognizes both horseshoe crab and mammalian B response elements. CrI B interacts with CrNF B and inhibits its nuclear translocation and DNA-binding activity. The activation of the CrNF B is autoregulated by a feedback mechanism mediated by CrI B, the natural inhibitor of CrNF B. We further show that Gram-negative bacteria infection causes rapid degradation of CrI B and nuclear translocation of CrNF B. Infection also leads to an increase in the B-binding activity and up-regulation of immune-related gene expression, like inducible nitric oxide synthase and Factor C, an LPS-activated serine protease. Altogether, our study shows that, although absent in C. elegans, the NF-B͞I B signaling cascade remains well conserved from horseshoe crab to humans, playing an archaic but fundamental role in regulating the expression of critical immune defense molecules.conservation and coevolution ͉ horseshoe crab ͉ infection and immune response ͉ transcriptional control T he family of NF-B transcription factors plays an indispensable role in immunity, inflammation, apoptosis, development, and differentiation (1, 2). NF-B dimers are held in an inactive cytoplasmic complex with a family of inhibitory proteins, the I Bs. Degradation of I Bs permits nuclear translocation of NF-B, where they stimulate the transcription of various immune-related genes (1). In Drosophila melanogaster, NF-B homologues (Dorsal, Dif, and Relish) are responsible for regulating several biological roles, including humoral immunity and development (3, 4). These important and diverse functions make NF-B one of the best-studied transcriptional factors in biology (2). Unexpectedly, in Caenorhabditis elegans, the NF-B protein is absent, and similar functional homologues (Toll, Traf, Cactus) are not involved in innate immune response (5). This led to the suggestion that the p38 mitogen-activated protein kinase pathway, which mediates the immune response in C. elegans, is the ancestral signaling pathway of the common ancestor of nematodes, arthropods, and vertebrates, predating the evolution of the NF-B immune signaling pathway (6). Thus, the ancient origin of the NF-B signaling pathway is still a conundrum, and it remains unclear whether the similarities between Drosophila and the human NF-B pathway have resulted from convergent evolution or reflect common ancestral pathways. Therefore, additional information on ...

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A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans

Abstract: In C. elegans, tol-1 is important for development and pathogen recognition, as is Toll in Drosophila, but remarkably for the latter rôle, it functions in the context of a behavioral mechanism that keeps worms away from potential danger.

Cited by 377 publications

References 71 publications

Generation and modulation of chemosensory behaviors in C. elegans

Generation and modulation of chemosensory behaviors in C. elegans

Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response

Evidence for the ancient origin of the NF-κB/IκB cascade: Its archaic role in pathogen infection and immunity

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