@article{8808ed4ec69a4103b954c6aff734bec1,
title = "WWP-1 is a novel modulator of the DAF-2 insulin-like signaling network involved in pore-forming toxin cellular defenses in Caenorhabditis elegans",
abstract = "Pore-forming toxins (PFTs) are the single largest class of bacterial virulence factors. The DAF-2 insulin/insulin-like growth factor-1 signaling pathway, which regulates lifespan and stress resistance in Caenorhabditis elegans, is known to mutate to resistance to pathogenic bacteria. However, its role in responses against bacterial toxins and PFTs is as yet unexplored. Here we reveal that reduction of the DAF-2 insulin-like pathway confers the resistance of Caenorhabditis elegans to cytolitic crystal (Cry) PFTs produced by Bacillus thuringiensis. In contrast to the canonical DAF-2 insulin-like signaling pathway previously defined for aging and pathogenesis, the PFT response pathway diverges at 3-phosphoinositide-dependent kinase 1 (PDK-1) and appears to feed into a novel insulin-like pathway signal arm defined by the WW domain Protein 1 (WWP-1). In addition, we also find that WWP-1 not only plays an important role in the intrinsic cellular defense (INCED) against PFTs but also is involved in innate immunity against pathogenic bacteria Pseudomonas aeruginosa and in lifespan regulation. Taken together, our data suggest that WWP-1 and DAF-16 function in parallel within the fundamental DAF-2 insulin/IGF-1 signaling network to regulate fundamental cellular responses in C. elegans.",
author = "Chen, {Chang Shi} and Audrey Bellier and Kao, {Cheng Yuan} and Yang, {Ya Luen} and Chen, {Huan Da} and Los, {Ferdinand C.O.} and Aroian, {Raffi V.}",
note = "Funding Information: Some Caenorhabditis elegans strains used in this work were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH National Center for Research Resources (NCRR). C. elegans strains were maintained on NG plates using Escherichia coli strain OP50 as the food source . Strains used in this study were wild-type Bristol strain N2, daf-2(e1370), age-1(hx546), aap-1(m889), daf-18(e1375), pdk-1(sa680), pdk-1(sa709), pdk-1(mg142), akt-1(ok525), akt-1(sa573), akt-1(mg144), akt-2(ok393), sgk-1(ok538), daf-16(mu86), daf-2(e1370);daf-16(mu86), bre-3(ye28), rrf-3(pk1426), rrf-3(pk1426); glp-4(bn2), pcm-1(qa201), wwp-1(ok1102), wwp-1(gk372), and wwp-1(gk397) were each backcrossed at least 4 times. Bacteria expressing dsRNA directed against bre-3 and wwp-1 were part of a C. elegans RNAi library in E. coli strain HT115 (Geneservice, Cambridge U.K.). All RNAi clones have been confirmed by plasmid DNA sequencing. Escherichia coli HT115 transformed with the pAD48 construct, which expresses dsRNA targeting the daf-2 gene, was kindly provided by A. Dillin (Salk Institute, San Diego) . All bacterial strains were cultured under standard conditions. ",
year = "2010",
month = mar,
day = "2",
doi = "10.1371/journal.pone.0009494",
language = "English",
volume = "5",
journal = "PloS one",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",
}