Abstract
Sphingolipid signaling in Caenorhabditis elegans is vital for sensing environmental change and effecting appropriate cellular response. Many molecular components in sphingolipid intermediary metabolism are conserved throughout evolution. Here we review use of C. elegans as a model system for conducting sphingolipid-based scientific investigation, which has helped us better understand vital roles these remarkable lipids play in human metabolism and disease.
Acknowledgments
We gratefully appreciate the assistance of Joerg Thomas Hannich and Howard Riezman in writing the section describing structural differences between C. elegans and mammalian sphingolipids.
References
Aguilera-Romero, A., Gehin, C., and Riezman, H. (2014). Sphingolipid homeostasis in the web of metabolic routes. Biochim. Biophys. Acta 1841, 647–656.10.1016/j.bbalip.2013.10.014Suche in Google Scholar PubMed
Chan, J.P. and Sieburth, D. (2012). Localized sphingolipid signaling at presynaptic terminals is regulated by calcium influx and promotes recruitment of priming factors. J. Neurosci. 32, 17909–17920.10.1523/JNEUROSCI.2808-12.2012Suche in Google Scholar PubMed PubMed Central
Chan, J.P., Hu, Z., and Sieburth, D. (2012). Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release. Genes Dev. 26, 1070–1085.10.1101/gad.188003.112Suche in Google Scholar PubMed PubMed Central
Chen, F., Hersh, B.M., Conradt, B., Zhou, Z., Riemer, D., Gruenbaum, Y., and Horvitz, H.R. (2000). Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science 287, 1485–1489.10.1126/science.287.5457.1485Suche in Google Scholar PubMed
Chitwood, D.J., Lusby, W.R., Thompson, M.J., Kochansky, J.P., and Howarth, O.W. (1995). The glycosylceramides of the nematode Caenorhabditis elegans contain an unusual, branched-chain sphingoid base. Lipids 30, 567–573.10.1007/BF02537032Suche in Google Scholar PubMed
Deng, X., Yin, X., Allan, R., Lu, D.D., Maurer, C.W., Haimovitz- Friedman, A., Fuks, Z., Shaham, S., and Kolesnick, R. (2008). Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science 322, 110–115.10.1126/science.1158111Suche in Google Scholar PubMed PubMed Central
Entchev, E.V., Schwudke, D., Zagoriy, V., Matyash, V., Bogdanova, A., Habermann, B., Zhu, L., Shevchenko, A., and Kurzchalia, T.V. (2008). LET-767 is required for the production of branched chain and long chain fatty acids in Caenorhabditis elegans. J. Biol. Chem. 283, 17550–17560.10.1074/jbc.M800965200Suche in Google Scholar PubMed
Futerman, A.H. and Riezman, H. (2005). The ins and outs of sphingolipid synthesis. Trends Cell. Biol. 15, 312–318.10.1016/j.tcb.2005.04.006Suche in Google Scholar PubMed
Fyrst, H. and Saba, J.D. (2010). An update on sphingosine-1-phosphate and other sphingolipid mediators. Nat. Chem. Biol. 6, 489–497.10.1038/nchembio.392Suche in Google Scholar PubMed PubMed Central
Gulbins, E. and Li, P. L. (2006). Physiological and pathophysiological aspects of ceramide. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R11–26.10.1152/ajpregu.00416.2005Suche in Google Scholar PubMed
Gulbins, E., Palmada, M., Reichel, M., Luth, A., Bohmer, C., Amato, D., Muller, C.P., Tischbirek, C.H., Groemer, T.W., Tabatabai, G., et al. (2013). Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs. Nat. Med. 19, 934–938.10.1038/nm.3214Suche in Google Scholar
Howell, J.J. and Manning, B.D. (2011). mTOR couples cellular nutrient sensing to organismal metabolic homeostasis. Trends Endocrinol. Metab. 22, 94–102.10.1016/j.tem.2010.12.003Suche in Google Scholar
Hua, G. and Kolesnick, R. (2013). Using ASMase knockout mice to model human diseases. Handb. Exp. Pharmacol. 29–54.10.1007/978-3-7091-1511-4_2Suche in Google Scholar
Ichikawa, S. and Hirabayashi, Y. (1998). Glucosylceramide synthase and glycosphingolipid synthesis. Trends Cell Biol. 8, 198–202.10.1016/S0962-8924(98)01249-5Suche in Google Scholar
Jennemann, R., Kaden, S., Sandhoff, R., Nordstrom, V., Wang, S., Volz, M., Robine, S., Amen, N., Rothermel, U., Wiegandt, H., et al. (2012). Glycosphingolipids are essential for intestinal endocytic function. J. Biol. Chem. 287, 32598–32616.10.1074/jbc.M112.371005Suche in Google Scholar PubMed PubMed Central
Jiang, J.C., Kirchman, P.A., Zagulski, M., Hunt, J., and Jazwinski, S.M. (1998). Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human. Genome Res. 8, 1259–1272.10.1101/gr.8.12.1259Suche in Google Scholar PubMed
Kim, Y. and Sun, H. (2012). ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target. PLoS One 7, e45890.10.1371/journal.pone.0045890Suche in Google Scholar PubMed PubMed Central
Lee, M.J., Van Brocklyn, J.R., Thangada, S., Liu, C.H., Hand, A.R., Menzeleev, R., Spiegel, S., and Hla, T. (1998). Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science 279, 1552–1555.10.1126/science.279.5356.1552Suche in Google Scholar PubMed
Leipelt, M., Warnecke, D., Zahringer, U., Ott, C., Muller, F., Hube, B., and Heinz, E. (2001). Glucosylceramide synthases, a gene family responsible for the biosynthesis of glucosphingolipids in animals, plants, and fungi. J. Biol. Chem. 276, 33621–33629.10.1074/jbc.M104952200Suche in Google Scholar PubMed
Lin, X., Hengartner, M.O., and Kolesnick, R. (1998). Caenorhabditis elegans contains two distinct acid sphingomyelinases. J. Biol. Chem. 273, 14374–14379.10.1074/jbc.273.23.14374Suche in Google Scholar PubMed
Liu, Y., Samuel, B.S., Breen, P. C., and Ruvkun, G. (2014). Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature 508, 406–410.10.1038/nature13204Suche in Google Scholar PubMed PubMed Central
Marza, E., Simonsen, K.T., Faergeman, N.J., and Lesa, G.M. (2009). Expression of ceramide glucosyltransferases, which are essential for glycosphingolipid synthesis, is only required in a small subset of C. elegans cells. J. Cell Sci. 122, 822–833.Suche in Google Scholar
Mendel, J., Heinecke, K., Fyrst, H., and Saba, J.D. (2003). Sphingosine phosphate lyase expression is essential for normal development in Caenorhabditis elegans. J. Biol. Chem. 278, 22341–22349.10.1074/jbc.M302857200Suche in Google Scholar PubMed
Menuz, V., Howell, K.S., Gentina, S., Epstein, S., Riezman, I., Fornallaz-Mulhauser, M., Hengartner, M.O., Gomez, M., Riezman, H. and Martinou, J.C. (2009). Protection of C. elegans from anoxia by HYL-2 ceramide synthase. Science 324, 381–384.10.1126/science.1168532Suche in Google Scholar PubMed
Mosbech, M.B., Kruse, R., Harvald, E.B., Olsen, A.S., Gallego, S.F., Hannibal-Bach, H.K., Ejsing, C.S., and Faergeman, N.J. (2013). Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. PLoS One 8, e70087.10.1371/journal.pone.0070087Suche in Google Scholar PubMed PubMed Central
Mullen, T.D. and Obeid, L.M. (2012). Ceramide and apoptosis: exploring the enigmatic connections between sphingolipid metabolism and programmed cell death. Anticancer Agents Med. Chem. 12, 340–363.10.2174/187152012800228661Suche in Google Scholar PubMed
Neklesa, T.K. and Davis, R.W. (2009). A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex. PLoS Genet. 5, e1000515.10.1371/journal.pgen.1000515Suche in Google Scholar PubMed PubMed Central
Nelson, W.J. (2003). Adaptation of core mechanisms to generate cell polarity. Nature 422, 766–774.10.1038/nature01602Suche in Google Scholar PubMed PubMed Central
Nomura, K.H., Murata, D., Hayashi, Y., Dejima, K., Mizuguchi, S., Kage-Nakadai, E., Gengyo-Ando, K., Mitani, S., Hirabayashi, Y., Ito, M., et al. (2011). Ceramide glucosyltransferase of the nematode Caenorhabditis elegans is involved in oocyte formation and in early embryonic cell division. Glycobiology 21, 834–848.10.1093/glycob/cwr019Suche in Google Scholar PubMed
Obeid, L.M., Linardic, C.M., Karolak, L.A., and Hannun, Y.A. (1993). Programmed cell death induced by ceramide. Science 259, 1769–1771.10.1126/science.8456305Suche in Google Scholar PubMed
Oskouian, B. and Saba, J.D. (2004). Death and taxis: what non-mammalian models tell us about sphingosine-1-phosphate. Semin. Cell. Dev. Biol. 15, 529–540.10.1016/j.semcdb.2004.05.009Suche in Google Scholar PubMed
Saba, J.D. and Hla, T. (2004). Point-counterpoint of sphingosine 1-phosphate metabolism. Circ. Res. 94, 724–734.10.1161/01.RES.0000122383.60368.24Suche in Google Scholar
Sieburth, D., Ch’ng, Q., Dybbs, M., Tavazoie, M., Kennedy, S., Wang, D., Dupuy, D., Rual, J. F., Hill, D.E., Vidal, M., et al. (2005). Systematic analysis of genes required for synapse structure and function. Nature 436, 510–517.10.1038/nature03809Suche in Google Scholar
Sonnichsen, 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, 462–469.10.1038/nature03353Suche in Google Scholar
Spassieva, S., Seo, J.G., Jiang, J.C., Bielawski, J., Alvarez-Vasquez, F., Jazwinski, S.M., Hannun, Y.A., and Obeid, L.M. (2006). Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity. J. Biol. Chem. 281, 33931–33938.10.1074/jbc.M608092200Suche in Google Scholar
Spiegel, S., English, D. and Milstien, S. (2002). Sphingosine 1-phosphate signaling: providing cells with a sense of direction. Trends Cell Biol. 12, 236–242.10.1016/S0962-8924(02)02277-8Suche in Google Scholar
Spiegel, S. and Milstien, S. (2002). Sphingosine 1-phosphate, a key cell signaling molecule. J. Biol. Chem. 277, 25851–25854.10.1074/jbc.R200007200Suche in Google Scholar PubMed
Taha, T.A., Kitatani, K., El-Alwani, M., Bielawski, J., Hannun, Y.A., and Obeid, L.M. (2006). Loss of sphingosine kinase-1 activates the intrinsic pathway of programmed cell death: modulation of sphingolipid levels and the induction of apoptosis. FASEB J. 20, 482–484.10.1096/fj.05-4412fjeSuche in Google Scholar PubMed
Tedesco, P., Jiang, J., Wang, J., Jazwinski, S.M., and Johnson, T.E. (2008). Genetic analysis of hyl-1, the C. elegans homolog of LAG1/LASS1. Age (Dordr) 30, 43–52.10.1007/s11357-008-9046-3Suche in Google Scholar PubMed PubMed Central
Ternes, P., Feussner, K., Werner, S., Lerche, J., Iven, T., Heilmann, I., Riezman, H., and Feussner, I. (2011). Disruption of the ceramide synthase LOH1 causes spontaneous cell death in Arabidopsis thaliana. New Phytol. 192, 841–854.10.1111/j.1469-8137.2011.03852.xSuche in Google Scholar PubMed
van Meer, G. and Simons, K. (1988). Lipid polarity and sorting in epithelial cells. J. Cell Biochem. 36, 51–58.10.1002/jcb.240360106Suche in Google Scholar PubMed
Wei, J., Yerokun, T., Leipelt, M., Haynes, C. A., Radhakrishna, H., Momin, A., Kelly, S., Park, H., Wang, E., Carton, J.M., et al. (2009). Serine palmitoyltransferase subunit 1 is present in the endoplasmic reticulum, nucleus and focal adhesions, and functions in cell morphology. Biochim. Biophys. Acta 1791, 746–756.10.1016/j.bbalip.2009.03.016Suche in Google Scholar
Williams, R.D., Wang, E. and Merrill, A.H., Jr. (1984). Enzymology of long-chain base synthesis by liver: characterization of serine palmitoyltransferase in rat liver microsomes. Arch. Biochem. Biophys. 228, 282–291.10.1016/0003-9861(84)90069-9Suche in Google Scholar
Yan, N., Gu, L., Kokel, D., Chai, J., Li, W., Han, A., Chen, L., Xue, D., and Shi, Y. (2004). Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol. Cell 15, 999–1006.10.1016/j.molcel.2004.08.022Suche in Google Scholar PubMed
Zhang, H., Abraham, N., Khan, L.A., Hall, D.H., Fleming, J.T., and Gobel, V. (2011). Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis. Nat.Cell Biol. 13, 1189–1201.10.1038/ncb2328Suche in Google Scholar PubMed PubMed Central
Zhu, H., Shen, H., Sewell, A.K., Kniazeva, M., and Han, M. (2013). A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans. elife 2, e00429.10.7554/eLife.00429Suche in Google Scholar PubMed PubMed Central
©2015 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: Molecular Medicine of Sphingolipids
- HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
- The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
- Sphingolipids in viral infection
- Tackling the biophysical properties of sphingolipids to decipher their biological roles
- Ceramide and sphingosine in pulmonary infections
- Molecular mechanisms of erythrocyte aging
- Sphingolipids in liver injury, repair and regeneration
- Ultrasound-stimulated microbubble enhancement of radiation response
- Innate immune responses in the brain of sphingolipid lysosomal storage diseases
- Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
- The role of sphingolipids in endothelial barrier function
- The effect of altered sphingolipid acyl chain length on various disease models
- Secretory sphingomyelinase in health and disease
- Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
- Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
- The molecular medicine of acid ceramidase
- Caenorhabditis elegans as a model to study sphingolipid signaling
- S1PR4 is required for plasmacytoid dendritic cell differentiation
- Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
- Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
- Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
- Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
- Obituary
- The life and work of Dr. Robert Bittman (1942–2014)
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: Molecular Medicine of Sphingolipids
- HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
- The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
- Sphingolipids in viral infection
- Tackling the biophysical properties of sphingolipids to decipher their biological roles
- Ceramide and sphingosine in pulmonary infections
- Molecular mechanisms of erythrocyte aging
- Sphingolipids in liver injury, repair and regeneration
- Ultrasound-stimulated microbubble enhancement of radiation response
- Innate immune responses in the brain of sphingolipid lysosomal storage diseases
- Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
- The role of sphingolipids in endothelial barrier function
- The effect of altered sphingolipid acyl chain length on various disease models
- Secretory sphingomyelinase in health and disease
- Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
- Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
- The molecular medicine of acid ceramidase
- Caenorhabditis elegans as a model to study sphingolipid signaling
- S1PR4 is required for plasmacytoid dendritic cell differentiation
- Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
- Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
- Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
- Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
- Obituary
- The life and work of Dr. Robert Bittman (1942–2014)