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.
authors.affiliation: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chang-Shi
authors.initials: CS
authors.lastname: Chen
authors.forename: Audrey
authors.initials: A
authors.lastname: Bellier
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Kao
authors.forename: Ya-Luen
authors.initials: YL
authors.lastname: Yang
authors.forename: Huan-Da
authors.initials: HD
authors.lastname: Chen
authors.forename: Ferdinand C O
authors.initials: FC
authors.lastname: Los
authors.forename: Raffi V
authors.initials: RV
authors.lastname: Aroian
mesh_terms: D000375:Aging; D000818:Animals; D001413:Bacillus thuringiensis / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism* / Q000502:physiology*; D005786:Gene Expression Regulation; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D034622:RNA Interference; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*; D037521:Virulence Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D037521:Virulence Factors; C413402:wwp-1 protein, C elegans; D044767:Ubiquitin-Protein Ligases; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin