Skip to main content
Log in

Cholesterol-responsive metabolic proteins are required for larval development in Caenorhabditis elegans

  • Research Article
  • Published:
Molecules and Cells

Abstract

Caenorhabditis elegans, a cholesterol auxotroph, showed defects in larval development upon cholesterol starvation (CS) in a previous study. To identify cholesterol-responsive proteins likely responsible for the larval arrest upon CS, a comparative proteomic analysis was performed between C. elegans grown in normal medium supplemented with cholesterol (CN) and those grown in medium not supplemented with cholesterol (cholesterol starvation, CS). Our analysis revealed significant change (more than 2.2-fold, p < 0.05) in nine proteins upon CS. Six proteins were down-regulated [CE01270 (EEF-1A.1), CE08852 (SAMS-1), CE11068 (PMT-2), CE09015 (ACDH-1), CE12564 (R07H5.8), and CE09655 (RLA-0)], and three proteins were up-regulated [CE29645 (LEC-1), CE16576 (LEC-5), and CE01431 (NEX-1)]. RNAi phenotypes of two of the down-regulated genes, R07H5.8 (adenosine kinase) and rla-0 (ribosomal protein), in CN were similar to that of larval arrest in CS, and RNAi of a down-regulated gene, R07H5.8, in CS further enhanced the effects of CS, suggesting that down-regulation of these genes is likely responsible for the larval arrest in CS. All three up-regulated genes contain putative DAF-16 binding sites and mRNA levels of these three genes were all decreased in daf-16 mutants in CN, suggesting that DAF-16 activates expression of these genes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ahn, D.H., Singaravelu, G., Lee, S., Ahnn, J., and Shim, Y.H. (2006). Functional and phenotypic relevance of differentially expressed proteins in calcineurin mutants of Caenorhabditis elegans. Proteomics 6, 1340–1350.

    Article  PubMed  CAS  Google Scholar 

  • Arur, S., Uche, U.E., Rezaul, K., Fong, M., Scranton, V., Cowan, A.E., Mohler, W., and Han, D.K. (2003). Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev. Cell 4, 587–598.

    Article  PubMed  CAS  Google Scholar 

  • Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71–94.

    PubMed  CAS  Google Scholar 

  • Chiang, P.K., Gordon, R.K., Tal, J., Zeng, G.C., Doctor, B.P., Pardhasaradhi, K., and McCann, P.P. (1996). S-adenosylmethionine and methylation. FASEB J. 10, 471–480.

    PubMed  CAS  Google Scholar 

  • Choi, B.K., Chitwood, D.J., and Paik, Y.K. (2003). Proteomic changes during disturbance of cholesterol metabolism by azacoprostane treatment in Caenorhabditis elegans. Mol. Cell. Proteomics 2, 1086–1095.

    Article  PubMed  CAS  Google Scholar 

  • Clayton, P.T. (1998). Disorders of cholesterol biosynthesis. Arch. Dis. Child. 78, 185–189.

    Article  PubMed  CAS  Google Scholar 

  • Farese R.V., and Jr, Herz, J. (1998). Cholesterol metabolism and embryogenesis. Trends Genet. 14, 115–120.

    Article  PubMed  CAS  Google Scholar 

  • Gerisch, B., Weitzel, C., Kober-Eisermann, C., Rottiers, V., and Antebi, A. (2001). A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev. Cell 1, 841–851.

    Article  PubMed  CAS  Google Scholar 

  • Gottschalk, A., Almedom, R.B., Schedletzky, T., Anderson, S.D., Yates, J.R. 3rd, and Schafer, W.R. (2005). Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans. EMBO J. 24, 2566–2578.

    Article  PubMed  CAS  Google Scholar 

  • Gygi, S.P., Rochon, Y., Franza, B.R., and Aebersold, R. (1999). Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol. 19, 1720–1730.

    PubMed  CAS  Google Scholar 

  • Iwamoto, M., Taguchi, C., Sasaguri, K., Kubo, K., Horie, H., Yamamoto, T., Onozuka, M., Sato, S., and Kadoua, T. (2010). The galectin-1 level in serum as a novel marker for stress. Glycoconj. J. 27, 419–425.

    Article  PubMed  CAS  Google Scholar 

  • Jeong, P.Y., Na, K., Jeong, M.J., Chitwood, D., Shim, Y.H., and Paik, Y.K. (2009). Proteomic analysis of Caenorhabditis elegans. Methods Mol. Biol. 519, 145–169.

    PubMed  CAS  Google Scholar 

  • Jeong, M.W., Kawasaki, I., and Shim, Y.H. (2010). A circulatory transcriptional regulation among daf-9, daf-12, and daf-16 mediates larval development upon cholesterol starvation in Caenorhabditis elegans. Dev. Dynam. 239, 1931–1940.

    Article  CAS  Google Scholar 

  • Kawasaki, I., Jeong, M.W., and Shim, Y.H. (2011). Regulation of sperm-specific proteins by IFE-1, a germline-specific homolog of eIF4E, in C. elegans. Mol. Cells 31, 191–197.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., Na, K., Lee, H.J., Lee, E.Y., and Paik, Y.K. (2011). Contribution of sams-1 and pmt-1 to lipid homoeostasis in adult Caenorhabditis elegans. J. Biochem. 149, 529–538.

    Article  PubMed  CAS  Google Scholar 

  • Lozano, R., Chitwood, D.J., Lusby, W.R., Thompson, M.J., Svoboda, J.A., and Patterson, G.W. (1984). Comparative effects of growth inhibitors on sterol metabolism in the nematode Caenorhabditis elegans. Comp. Biochem. Physiol. 79, 21–26.

    CAS  Google Scholar 

  • Matyash, V., Entchev, E.V., Mende, F., Wilsch-Brauninger, M., Thiele, C., Schmidt, A.W., Knölker, H.J., Ward, S., and Kurzchalia, T.V. (2004). Sterol-derived hormone(s) controls entry into diapause in Caenorhabditis elegans by consecutive activation of DAF-12 and DAF-16. PLoS Biol. 2, e280.

    Article  PubMed  Google Scholar 

  • Nemato-Sasaki, Y., Hayama, K., Ohya, H., Arata, Y., Kaneko, M.K., Sitou, N., Hirabayashi, J., and Kasai, K. (2008). Caenorhabditis elegans galectins LEC-1-LEC-11: structural features and sugarbinding properties. Biochim. Biophys. Acta 1780, 1131–1142.

    Article  Google Scholar 

  • Oh, S.W., Mukhopadhyay, A., Dixit B.L., Raha, T., Green, M.R., and Tissenbaum, H.A. (2006). Identification of direct DAF-16 tar-gets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nat. Genet. 38, 251–257.

    Article  PubMed  Google Scholar 

  • Pace, K.E., Lebestky, T., Hummel, T., Arnoux, P., Kwan, K., and Baum, L.G. (2002). Characterization of a novel Drosophila melanogaster galectin. J. Biol. Chem. 277, 13091–13098.

    Article  PubMed  CAS  Google Scholar 

  • Paik, Y.K., Jeong, S.K., Lee, E.Y., Jeong, P.Y., Shim, Y.H. (2006). C. elegans: an invaluable model organism for the proteomics studies of the cholesterol-mediated signaling pathway. Expert Rev. Proteomics 3, 439–453.

    CAS  Google Scholar 

  • Rual, J.F., Ceron, J., Koreth, J., Hao, T., Nicot, A.S., Hirozane-Kishikawa, T., Vandenhaute, J., Orkin, S.H., Hill, D.E., van den Heuvel, S., et al. (2004). Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res. 14, 2162–2168.

    Article  PubMed  CAS  Google Scholar 

  • Satoh, A., Hazuki, M., Kojima, K., Hirabayashi, J., and Matsumoto, I. (2000). Ligand-binding properties of annexin from Caenorhabditis elegans (Annexin XVI, Nex-1). J. Biochem. 128, 377–381.

    Article  PubMed  CAS  Google Scholar 

  • Seppo, A., and Tiemeyer, M. (2000). Function and structure of Drosophila glycans. Glycobiology 10, 751–760.

    Article  PubMed  CAS  Google Scholar 

  • Shim, Y.H., and Paik, Y.K. (2010). Caenorhabditis elegans proteomics comes of age. Proteomics 10, 846–857.

    Article  PubMed  CAS  Google Scholar 

  • Simmer, F., Moorman, C., van der Linden, A.M., Kuijk, E., van den Berghe, P.V., Kamath, R.S., Fraser, A.G., Ahringer, J., and Plasterk, R.H. (2003). Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol. 1, E12.

    Article  PubMed  Google Scholar 

  • Sönnichsen, B., Koski, L.B., Walsh, A., Marschall, P., Neumann, B., Brehm, M., Alleaume, A.M., Artelt, J., Bettencourt, P., Cassin, E., et al. (2005). Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434, 462–469.

    Article  PubMed  Google Scholar 

  • Tabuse, Y., Nabetani, T., and Tsugita, A. (2005). Proteomic analysis of protein expression profiles during Caenorhabditis elegans development using two-dimensional difference gel electrophoresis. Proteomics 5, 2876–2891.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yhong-Hee Shim.

About this article

Cite this article

Kawasaki, I., Jeong, MH., Yun, YJ. et al. Cholesterol-responsive metabolic proteins are required for larval development in Caenorhabditis elegans . Mol Cells 36, 410–416 (2013). https://doi.org/10.1007/s10059-013-0170-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10059-013-0170-2

Keywords

Navigation