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Lipid signalling couples translational surveillance to systemic detoxification in Caenorhabditis elegans

Nature Cell Biology volume 17, pages 12941303 (2015) | Download Citation

Abstract

Translation in eukaryotes is followed to detect toxins and virulence factors and coupled to the induction of defence pathways. Caenorhabditis elegans germline-specific mutations in translation components are detected by this system to induce detoxification and immune responses in distinct somatic cells. An RNA interference screen revealed gene inactivations that act at multiple steps in lipid biosynthetic and kinase pathways upstream of MAP kinase to mediate the systemic communication of translation defects to induce detoxification genes. Mammalian bile acids can rescue the defect in detoxification gene induction caused by C. elegans lipid biosynthetic gene inactivations. Extracts prepared from C. elegans with translation deficits but not from the wild type can also rescue detoxification gene induction in lipid-biosynthesis-defective strains. These eukaryotic antibacterial countermeasures are not ignored by bacteria: particular bacterial species suppress normal C. elegans detoxification responses to mutations in translation factors.

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Acknowledgements

Strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), and S. Mitani of the Japanese National Bioresources Project. This work was supported in part by the National Institutes of Health Grant AG043184-16A (to G.R.). Thanks to D. Coil and J. Eisen for providing Kocuria species.

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Affiliations

  1. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

    • J. Amaranath Govindan
    • , Elamparithi Jayamani
    • , Xinrui Zhang
    • , Peter Breen
    • , Jonah Larkins-Ford
    •  & Gary Ruvkun
  2. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • J. Amaranath Govindan
    •  & Gary Ruvkun
  3. Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA

    • Elamparithi Jayamani
    •  & Eleftherios Mylonakis

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Contributions

J.A.G. and G.R. conceived the project. E.J. and E.M. provided the microbes used in the experiments. E.J. carried out the bacterial suppression experiments. J.L.-F. helped with the data collection and analysis. X.Z. conducted the qRT-PCR experiments. P.B. constructed transgenic pmk-1::mcherry lines. J.A.G. and G.R. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gary Ruvkun.

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DOI

https://doi.org/10.1038/ncb3229