Abstract
The Caenorhabditis elegans DAF-16 transcription factor is critical for diverse biological processes, particularly longevity and stress resistance. Disruption of the DAF-2 signaling cascade promotes DAF-16 activation, and confers resistance to killing by pathogenic bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. However, daf-16 mutants exhibit similar sensitivity to these bacteria as wild-type animals, suggesting that DAF-16 is not normally activated by these bacterial pathogens. In this report, we demonstrate that DAF-16 can be directly activated by fungal infection and wounding in wild-type animals, which is independent of the DAF-2 pathway. Fungal infection and wounding initiate the Gαq signaling cascade, leading to Ca(2+) release. Ca(2+) mediates the activation of BLI-3, a dual-oxidase, resulting in the production of reactive oxygen species (ROS). ROS then activate DAF-16 through a Ste20-like kinase-1/CST-1. Our results indicate that DAF-16 in the epidermis is required for survival after fungal infection and wounding. Thus, the EGL-30-Ca(2+)-BLI-3-CST-1-DAF-16 signaling represents a previously unknown pathway to regulate epidermal damage response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / immunology*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / immunology*
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Caenorhabditis elegans Proteins / metabolism
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Calcium Signaling / genetics
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Calcium Signaling / immunology
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Dermatomycoses / genetics
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Dermatomycoses / immunology*
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Dermatomycoses / metabolism
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Epidermis / immunology*
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Epidermis / metabolism
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Forkhead Transcription Factors
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GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
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GTP-Binding Protein alpha Subunits, Gq-G11 / immunology
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GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
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Gram-Positive Bacterial Infections / genetics
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Gram-Positive Bacterial Infections / immunology*
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Gram-Positive Bacterial Infections / metabolism
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Immunity, Innate*
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Oxidoreductases / genetics
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Oxidoreductases / immunology
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Oxidoreductases / metabolism
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Reactive Oxygen Species / immunology
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Reactive Oxygen Species / metabolism
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Skin Diseases, Bacterial / genetics
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Skin Diseases, Bacterial / immunology*
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Skin Diseases, Bacterial / metabolism
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription Factors / metabolism
Substances
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Caenorhabditis elegans Proteins
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Egl-30 protein, C elegans
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Forkhead Transcription Factors
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Reactive Oxygen Species
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Transcription Factors
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daf-16 protein, C elegans
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Bli-3 protein, C elegans
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Oxidoreductases
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GTP-Binding Protein alpha Subunits, Gq-G11
Grants and funding
This work was supported in part by a grant (2013CB127500 and 2012CB722208) from National Basic Research Program of China, a grant from the National Natural Science Foundation of China (311171365) and a grant from Yunnan Department of Science and Technology (2009CI045).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.