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The sterol modifying enzyme LET-767 is essential for growth, reproduction and development in Caenorhabditis elegans

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Abstract

The let-767 gene encodes a protein that is similar to mammalian steroid enzymes that are responsible for the reduction of 17-beta hydroxysteroid hormones. Caenorhabditis elegans is incapable of the de novo synthesis of cholesterol. Therefore, this free-living nematode must extract cholesterol from its environment and modify it to form steroid hormones that are necessary for its survival. C. elegans is unable to survive in the absence of supplemental cholesterol, and is therefore sensitive to cholesterol limitation. We show that a mutation in let-767 results in hypersensitivity to cholesterol limitation, supporting the hypothesis that LET-767 acts on a sterol derivative. Furthermore, let-767 mutants exhibit defects in embryogenesis, female reproduction and molting. Although ecdysone is the major molting hormone in insects, there is as yet no evidence for ecdysone synthesis in C. elegans, suggesting that a different hormone is required for molting in C. elegans. Our results suggest that LET-767 modifies a sterol hormone that is required both for embryogenesis and for later stages of development.

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Acknowledgements

We would like to thank Andrew Fire for providing the gfp vector and Alan Coulson for providing the cosmids. We would also like to thank the CGC for providing strains that were used in this study. This work was supported by National Science and Engineering Research Council Grant No. 31-611129

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Author notes

  1. L. M. Kuervers

    Present address: Department of Developmental Biology, Stanford University, 279 Campus Drive, Stanford, CA 94305, USA

  2. N. J. O'Neil

    Present address: Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

Authors and Affiliations

  1. Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada

    L. M. Kuervers, C. L. Jones, N. J. O'Neil & D. L. Baillie

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  1. L. M. Kuervers
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  2. C. L. Jones
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  3. N. J. O'Neil
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  4. D. L. Baillie
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Corresponding author

Correspondence to D. L. Baillie.

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Communicated by C. P. Hollenberg

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Kuervers, L.M., Jones, C.L., O'Neil, N.J. et al. The sterol modifying enzyme LET-767 is essential for growth, reproduction and development in Caenorhabditis elegans . Mol Genet Genomics 270, 121–131 (2003). https://doi.org/10.1007/s00438-003-0900-9

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  • DOI: https://doi.org/10.1007/s00438-003-0900-9

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