Establishing C. elegans as a Model to Study the Function of Vitamin A Metabolism
Keywords:
vitamin A, metabolism, model systemAbstract
Vitamin A is critical for cell development, maintaining a healthy immune system, regulating energy metabolism, and eyesight in mammals. In addition, abnormal levels contribute to obesity and cancer. While vitamin A plays these many roles, what is not well known is the impact of individual vitamin A metabolism genes at the cellular level. We asked if the roundworm C. elegans, an established animal model system with a sequenced genome and established methods for genetic and cellular analyses, is appropriate for the study of vitamin A metabolism. To determine if the C. elegans genome contains genes encoding potential vitamin A metabolism genes, we performed literature and database searches. We identified potential retinoid metabolism genes in the C. elegans genome. Furthermore, some of these genes share phenotypes with their mammalian homologs. These genes include cellular retinol-binding proteins, retinol dehydrogenases, retinal dehydrogenase, cellular retinoic acid-binding proteins, and retinoic acid receptors. However, many of these genes in C. elegans and mammals have no known mutant traits. We conclude that the roundworm C. elegans may be an excellent model organism for this investigation because all expected genes are conserved. Future research in C. elegans will define the functional conservation of the vitamin A metabolism pathway in C. elegans and will characterize the physiological relevance of altered and normal vitamin A metabolism at the cellular level.
References
Albalat, R. (2009). The retinoic acid machinery in invertebrates: ancestral elements and vertebrate innovations. Mol Cell Endocrinol, 313(1-2), 23-35. https://doi.org/10.1016/j.mce.2009.08.029
Arda, H. E., Taubert, S., MacNeil, L. T., Conine, C. C., Tsuda, B., Van Gilst, M., Sequerra, R., Doucette-Stamm, L., Yamamoto, K. R., & Walhout, A. J. (2010). Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network. Mol Syst Biol, 6, 367. https://doi.org/10.1038/msb.2010.23
Ashrafi, K., Chang, F. Y., Watts, J. L., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature, 421(6920), 268-272. https://doi.org/10.1038/nature01279
Baker, M. E. (1998). Evolution of mammalian 11beta- and 17beta-hydroxysteroid dehydrogenases-type 2 and retinol dehydrogenases from ancestors in Caenorhabditis elegans and evidence for horizontal transfer of a eukaryote dehydrogenase to E. coli. J Steroid Biochem Mol Biol, 66(5-6), 355-363. https://doi.org/10.1016/s0960-0760(98)00064-8
Belyaeva, O. V., Adams, M. K., Popov, K. M., & Kedishvili, N. Y. (2020). Generation of retinaldehyde for retinoic acid biosynthesis. Biomolecules, 10(1), Article 5. https://doi.org/10.3390/biom10010005
Benenati, G., Penkov, S., Muller-Reichert, T., Entchev, E. V., & Kurzchalia, T. V. (2009). Two cytochrome P450s in Caenorhabditis elegans are essential for the organization of eggshell, correct execution of meiosis and the polarization of embryo. Mech Dev, 126(5-6), 382-393. https://doi.org/10.1016/j.mod.2009.02.001
Carmi, I., Kopczynski, J. B., & Meyer, B. J. (1998). The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex. Nature, 396(6707), 168-173. https://doi.org/10.1038/24164
Chen, A. J., Li, J., Jannasch, A., Mutlu, A. S., Wang, M. C., & Cheng, J. X. (2018). Fingerprint stimulated Raman scattering imaging reveals retinoid coupling lipid metabolism and survival. Chemphyschem, 19(19), 2500-2506. https://doi.org/10.1002/cphc.201800545
Consortium, C. e. D. M. (2012). Large-scale screening for targeted knockouts in the Caenorhabditis elegans genome. G3 (Bethesda), 2(11), 1415-1425. https://doi.org/10.1534/g3.112.003830
Cui, Y., McBride, S. J., Boyd, W. A., Alper, S., & Freedman, J. H. (2007). Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity. Genome Biol, 8(6), R122. https://doi.org/10.1186/gb-2007-8-6-r122
Everts, H. B. (2012). Endogenous retinoids in the hair follicle and sebaceous gland. Biochim. Biophys. Acta., 1821(1), 222-229.
Folick, A., Oakley, H. D., Yu, Y., Armstrong, E. H., Kumari, M., Sanor, L., Moore, D. D., Ortlund, E. A., Zechner, R., & Wang, M. C. (2015). Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. Science, 347(6217), 83-86. https://doi.org/10.1126/science.1258857
Fraser, A. G., Kamath, R. S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M., & Ahringer, J. (2000). Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature, 408(6810), 325-330. https://doi.org/10.1038/35042517
Garofalo, A., Rowlinson, M. C., Amambua, N. A., Hughes, J. M., Kelly, S. M., Price, N. C., Cooper, A., Watson, D. G., Kennedy, M. W., & Bradley, J. E. (2003). The FAR protein family of the nematode Caenorhabditis elegans. Differential lipid binding properties, structural characteristics, and developmental regulation. J Biol Chem, 278(10), 8065-8074. https://doi.org/10.1074/jbc.M206278200
Green, R. M., Gally, F., Keeney, J. G., Alper, S., Gao, B., Han, M., Martin, R. J., Weinberger, A. R., Case, S. R., Minor, M. N., & Chu, H. W. (2009). Impact of cigarette smoke exposure on innate immunity: a Caenorhabditis elegans model. PLoS One, 4(8), e6860. https://doi.org/10.1371/journal.pone.0006860
Ha, M. K., Soo Cho, J., Baik, O. R., Lee, K. H., Koo, H. S., & Chung, K. Y. (2006). Caenorhabditis elegans as a screening tool for the endothelial cell-derived putative aging-related proteins detected by proteomic analysis. Proteomics, 6(11), 3339-3351. https://doi.org/10.1002/pmic.200500395
Hodgkin, J. (1986). Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes. Genetics, 114(1), 15-52. https://www.ncbi.nlm.nih.gov/pubmed/3770465
Kamath, R. S., Fraser, A. G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., Sohrmann, M., Welchman, D. P., Zipperlen, P., & Ahringer, J. (2003). Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature, 421(6920), 231-237. https://doi.org/10.1038/nature01278
Kostrouch, Z., Kostrouchova, M., & Rall, J. E. (1995). Steroid/thyroid hormone receptor genes in Caenorhabditis elegans. Proc Natl Acad Sci U S A, 92(1), 156-159. https://doi.org/10.1073/pnas.92.1.156
Kraemer, B. C., Burgess, J. K., Chen, J. H., Thomas, J. H., & Schellenberg, G. D. (2006). Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans. Hum Mol Genet, 15(9), 1483-1496. https://doi.org/10.1093/hmg/ddl067
Liang, B., Ferguson, K., Kadyk, L., & Watts, J. L. (2010). The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans. PLoS One, 5(3), e9869. https://doi.org/10.1371/journal.pone.0009869
Liu, J. L., Desjardins, D., Branicky, R., Agellon, L. B., & Hekimi, S. (2012). Mitochondrial oxidative stress alters a pathway in Caenorhabditis elegans strongly resembling that of bile acid biosynthesis and secretion in vertebrates. PLoS Genet, 8(3), e1002553. https://doi.org/10.1371/journal.pgen.1002553
Ma, D. K., Rothe, M., Zheng, S., Bhatla, N., Pender, C. L., Menzel, R., & Horvitz, H. R. (2013). Cytochrome P450 drives a HIF-regulated behavioral response to reoxygenation by C. elegans. Science, 341(6145), 554-558. https://doi.org/10.1126/science.1235753
MacNeil, L. T., Watson, E., Arda, H. E., Zhu, L. J., & Walhout, A. J. (2013). Diet-induced developmental acceleration independent of TOR and insulin in C. elegans. Cell, 153(1), 240-252. https://doi.org/10.1016/j.cell.2013.02.049
Maeda, I., Kohara, Y., Yamamoto, M., & Sugimoto, A. (2001). Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol, 11(3), 171-176. https://doi.org/10.1016/s0960-9822(01)00052-5
Menzel, R., Rodel, M., Kulas, J., & Steinberg, C. E. (2005). CYP35: xenobiotically induced gene expression in the nematode Caenorhabditis elegans. Arch Biochem Biophys, 438(1), 93-102. https://doi.org/10.1016/j.abb.2005.03.020
Minogue, A. L., Tackett, M. R., Atabakhsh, E., Tejada, G., & Arur, S. (2018). Functional genomic analysis identifies miRNA repertoire regulating C. elegans oocyte development. Nat Commun, 9(1), 5318. https://doi.org/10.1038/s41467-018-07791-w
Napoli, J. L. (2012). Physiological insights into all-trans-retinoic acid biosynthesis. Biochim. Biophys. Acta, Mol. Cell Biol. Lipids, 1821(1), 152-167. https://doi.org/10.1016./j.bbalip.2011.05.004
O'Rourke, D., Baban, D., Demidova, M., Mott, R., & Hodgkin, J. (2006). Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum. Genome Res, 16(8), 1005-1016. https://doi.org/10.1101/gr.50823006
O'Rourke, E. J., Kuballa, P., Xavier, R., & Ruvkun, G. (2013). Omega-6 polyunsaturated fatty acids extend life span through the activation of autophagy. Genes Dev, 27(4), 429-440. https://doi.org/10.1101/gad.205294.112
Piano, F., Schetter, A. J., Morton, D. G., Gunsalus, K. C., Reinke, V., Kim, S. K., & Kemphues, K. J. (2002). Gene clustering based on RNAi phenotypes of ovary-enriched genes in C. elegans. Curr Biol, 12(22), 1959-1964. https://doi.org/10.1016/s0960-9822(02)01301-5
Ross, A., & Harrison, E. (2007). Vitamin A: Nutritional aspects of retinoids and carotinoids. In J. Zampleni, J. W. Suttie, J. F. G. III, P. J. Stover, A. C. R. Harrison, & H. Earl (Eds.), Handbook of Vitamins (fourth ed., pp. 1-40). CRC Press. https://doi.org/10.1201/b15413-2
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., & Vidal, M. (2004). Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res, 14(10B), 2162-2168. https://doi.org/10.1101/gr.2505604
Shephard, F., Adenle, A. A., Jacobson, L. A., & Szewczyk, N. J. (2011). Identification and functional clustering of genes regulating muscle protein degradation from amongst the known C. elegans muscle mutants. PLoS One, 6(9), e24686. https://doi.org/10.1371/journal.pone.0024686
Simmer, F., Moorman, C., van der Linden, A. M., Kuijk, E., van den Berghe, P. V., Kamath, R. S., Fraser, A. G., Ahringer, J., & Plasterk, R. H. (2003). Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol, 1(1), E12. https://doi.org/10.1371/journal.pbio.0000012
Sonnichsen, B., Koski, L. B., Walsh, A., Marschall, P., Neumann, B., Brehm, M., Alleaume, A. M., Artelt, J., Bettencourt, P., Cassin, E., Hewitson, M., Holz, C., Khan, M., Lazik, S., Martin, C., Nitzsche, B., Ruer, M., Stamford, J., Winzi, M., Heinkel, R., Roder, M., Finell, J., Hantsch, H., Jones, S. J., Jones, M., Piano, F., Gunsalus, K. C., Oegema, K., Gonczy, P., Coulson, A., Hyman, A. A., & Echeverri, C. J. (2005). Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature, 434(7032), 462-469. https://doi.org/10.1038/nature03353
Tanumihardjo, S. A., Russell, R. M., Stephensen, C. B., Gannon, B. M., Craft, N. E., Haskell, M. J., Lietz, G., Schulze, K., & Raiten, D. J. (2016). Biomarkers of Nutrition for Development (BOND)-Vitamin A review. J Nutr, 146(9), 1816S-1848S. https://doi.org/10.3945/jn.115.229708
Trent, C., Tsuing, N., & Horvitz, H. R. (1983). Egg-laying defective mutants of the nematode Caenorhabditis elegans. Genetics, 104(4), 619-647. https://www.ncbi.nlm.nih.gov/pubmed/11813735
Wu, J., Xiang, H., Qi, Y., Yang, D., Wang, X., Sun, H., Wang, F., & Liu, B. (2014). Adaptive evolution of the STRA6 genes in mammalian. PLoS One, 9(9), e108388. https://doi.org/10.1371/journal.pone.0108388
Xu, M., Joo, H. J., & Paik, Y. K. (2011). Novel functions of lipid-binding protein 5 in Caenorhabditis elegans fat metabolism. J Biol Chem, 286(32), 28111-28118. https://doi.org/10.1074/jbc.M111.227165
Yilmaz, L. S., & Walhout, A. J. (2016). A Caenorhabditis elegans genome-scale metabolic network model. Cell Syst, 2(5), 297-311. https://doi.org/10.1016/j.cels.2016.04.012
Zhang, Y., Zou, X., Ding, Y., Wang, H., Wu, X., & Liang, B. (2013). Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans. BMC Genomics, 14, 164. https://doi.org/10.1186/1471-2164-14-164
Zhao, Z., Fang, L. L., Johnsen, R., & Baillie, D. L. (2004). ATP-binding cassette protein E is involved in gene transcription and translation in Caenorhabditis elegans. Biochem Biophys Res Commun, 323(1), 104-111. https://doi.org/10.1016/j.bbrc.2004.08.068
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