Ceramide synthases in mammalians, worms, and insects: Emerging schemes

Biomolecular Concepts

Volumn 1, Issue 5-6, 2010, Pages 411-422

  Voelzmann, André ^a   Bauer, Reinhard ^a  

^a UNIVERSITY OF BONN   (Germany)

Author keywords

apoptosis; Caenorhabditis elegans; Cancer; Ceramide synthase; Drosophila; homeodomain; LAG1 motif; Lipid homeostasis; Longevity

Indexed keywords

CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; EUKARYOTA; HEXAPODA; MAMMALIA;

EID: 80054885427     PISSN: 18685021     EISSN: 1868503X     Source Type: Journal    
DOI: 10.1515/bmc.2010.028     Document Type: Review

References (88)

1. Merrill AH. De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem 2002; 277: 25843-6.
2. Kolter T, Proia RL, Sandhoff K. Combinatorial ganglioside biosynthesis. J Biol Chem 2002; 277: 25859-62.
3. Hanada K. Discovery of the molecular machinery CERT for endoplasmic reticulum-to-Golgi trafficking of ceramide. Mol Cell Biochem 2006; 286: 23-31.
4. Dolgachev V, Farooqui MS, Kulaeva OI, Tainsky MA, Nagy B, Hanada K, Separovic D. De novo ceramide accumulation due to inhibition of its conversion to complex sphingolipids in apoptotic photosensitized cells. J Biol Chem 2004; 279: 23238-49.
5. Futerman AH, Riezman H. The ins and outs of sphingolipid synthesis. Trends Cell Biol 2005; 15: 312-8.
6. Dickson RC, Lester RL. Yeast sphingolipids. Biochim Biophys Acta 1999; 1426: 347-57.
7. Wells GB, Lester RL. The isolation and characterization of a mutant strain of Saccharomyces cerevisiae that requires a long chain base for growth and for synthesis of phosphosphingolipids. J Biol Chem 1983; 258: 10200-3.
8. Morell P, Radin NS. Specificity in ceramide biosynthesis from long chain bases and various fatty acyl coenzyme A's by brain microsomes. J Biol Chem 1970; 245: 342-50.
9. Guillas I, Kirchman PA, Chuard R, Pfefferli M, Jiang JC, Jazwinski SM, Conzelmann A. C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p. EMBO J 2001; 20: 2655-65.
10. Schorling S, Vallee B, Barz WP, Riezman H, Oesterhelt D. Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae. Mol Biol Cell 2001; 12: 3417-27.
11. D'Mello NP, Childress AM, Franklin DS, Kale SP, Pinswasdi C, Jazwinski SM. Cloning and characterization of LAG1, a longevity-assurance gene in yeast. J Biol Chem 1994; 269: 15451-9.
12. Jiang JC, Kirchman PA, Zagulski M, Hunt J, Jazwinski SM. Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human. Genome Res 1998; 8: 1259-72.
13. Lee SJ. Expression of growth/differentiation factor 1 in the nervous system: conservation of a bicistronic structure. Proc Natl Acad Sci USA 1998; 88: 4250-4.
14. Brandwagt BF, Mesbah LA, Takken FL, Laurent PL, Kneppers TJ, Hille J, Nijkamp HJ. A longevity assurance gene homolog of tomato mediates resistance to Alternaria alternata f. sp. lycopersici toxins and fumonisin B1. Proc Natl Acad Sci USA 2000; 97: 4961-6.
15. Bauer R, Voelzmann A, Breiden B, Schepers U, Farwanah H, Hahn I, Eckardt F, Sandhoff K, Hoch M. Schlank, a member of the ceramide synthase family controls growth and body fat in Drosophila. EMBO J 2009; 28: 3706-16.
16. Sonnhammer EL, Eddy SR, Durbin R. Pfam: a comprehensive database of protein domain families based on seed alignments. Proteins 1997; 28: 405-20.
17. Winter E, Ponting CP. TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains? Trends Biochem Sci 2002; 27: 381-3.
18. Venkataraman K, Futerman AH. Do longevity assurance genes containing Hox domains regulate cell development via ceramide synthesis? FEBS Lett 2002; 528: 3-4.
19. Spassieva S, Seo JG, Jiang JC, Bielawski J, Alvarez-Vasquez F, Jazwinski SM, Hannun YA, Obeid LM. Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity. J Biol Chem 2006; 10: 33931-8.
20. Kageyama-Yahara N, Riezman H. Transmembrane topology of ceramide synthase in yeast. Biochem J 2006; 398: 585-93.
21. Gehring WJ, Affolter M, Bürglin T. Homeodomain proteins. Annu Rev Biochem 1994; 63: 487-526.
22. Teufel A, Maass T, Galle PR, Malik N. The longevity assurance homologue of yeast lag1 (Lass) gene family. Int J Mol Med 2009; 23: 135-40.
23. Levy M, Futerman AH. Mammalian ceramide synthases. IUBMB Life 2010; 62: 347-56.
24. Venkataraman K, Riebeling C, Bodennec J, Riezman H, Allegood JC, Sullards MC, Merrill AH Jr, Futerman AH. Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro) ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. J Biol Chem 2002; 277: 35642-9.
25. Riebeling C, Allegood JC, Wang E, Merrill AH Jr, Futerman AH. Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J Biol Chem 2003; 278: 43452-9.
26. Mizutani Y, Kihara A, Igarashi Y. Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J 2006; 390: 263-71.
27. Mandon EC, Ehses I, Rother J, van Echten G, Sandhoff K. Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase in mouse liver. J Biol Chem 1992; 267: 11144-8.
28. Hirschberg K, Rodger J, Futerman AH. The long-chain sphingoid base of sphingolipids is acylated at the cytosolic surface of the endoplasmic reticulum in rat liver. Biochem J 1993; 15: 751-7.
29. White-Gilbertson S, Mullen T, Senkal C, Lu P, Ogretmen B, Obeid L, Voelkel-Johnson C. Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells. Oncogene 2009; 28: 1132-41.
30. Bionda C, Portoukalian J, Schmitt D, Rodriguez-Lafrasse C, Ardail D. Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria-associated membrane) and/or mitochondria? Biochem J 2004; 382: 527-33.
31. Koybasi S, Senkal CE, Sundararaj K, Spassieva S, Bielawski J, Osta W, Day TA, Jiang JC, Jazwinski SM, Hannun YA, Obeid LM, Ogretmen B. Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas. J Biol Chem 2004; 279: 44311-9.
32. Karahatay S, Thomas K, Koybasi S, Senkal CE, Elojeimy S, Liu X, Bielawski J, Day TA, Gillespie MB, Sinha D, Norris JS, Hannun YA, Ogretmen B. Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC): attenuation of C(18)-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis. Cancer Lett 2007; 256: 101-11.
33. Saddoughi SA, Song P, Ogretmen B. Roles of bioactive sphingolipids in cancer biology and therapeutics. Subcell Biochem 2008; 49: 413-40.
34. Schiffmann S, Sandner J, Birod K, Wobst I, Angioni C, Ruckhaberle E, Kaufmann M, Ackermann H, Lotsch J, Schmidt H, Geisslinger G, Grosch S. Ceramide synthases and ceramide levels are increased in breast cancer tissue. Carcinogenesis 2009; 30: 745-52.
35. Erez-Roman R, Pienik R, Futerman AH. Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression. Biochem Biophys Res Commun 2010; 391: 219-23.
36. Pan H, Qin WX, Huo KK, Wan DF, Yu Y, Xu ZG, Hu QD, Gu KT, Zhou XM, Jiang HQ, Zhang PP, Huang Y, Li YY, Gu JR. Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1. Genomics 2001; 77: 58-64.
37. Pewzner-Jung Y, Brenner O, Braun S, Laviad EL, Ben-Dor S, Feldmesser E, Horn-Saban S, Amann-Zalcenstein D, Raanan C, Berkutzki T, Erez-Roman R, Ben-David O, Levy M, Holzman D, Park H, Nyska A, Merrill AH Jr, Futerman AH. A critical role for ceramide synthase 2 in liver homeostasis: II. Insights into molecular changes leading to hepatopathy. J Biol Chem 2010; 285: 10911-23.
38. Imgrund S, Hartmann D, Farwanah H, Eckhardt M, Sandhoff R, Degen J, Gieselmann V, Sandhoff K, Willecke K. Adult ceramide synthase 2 (Cers2) deficient mice exhibit myelin sheath defects, cerebellar degeneration and hepatocarcinomas. J Biol Chem 2009; 284: 33549-60.
39. Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 2004; 4: 604-16.
40. Min J, Mesika A, Sivaguru M, Van Veldhoven PP, Alexander H, Futerman AH, Alexander S. (Dihydro)ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1. Mol Cancer Res 2007; 5: 801-12.
41. Rénert AF, Leprince P, Dieu M, Renaut J, Raes M, Bours V, Chapelle JP, Piette J, Merville MP, Fillet M. The proapoptotic C16-ceramide-dependent pathway requires the death-promoting factor Btf in colon adenocarcinoma cells. J Proteome Res 2009; 8: 4810-22.
42. Mesicek J, Lee H, Feldman T, Jiang X, Skobeleva A, Berdyshev EV, Haimovitz-Friedman A, Fuks Z, Kolesnick R. Ceramide synthases 2, 5, and 6 confer distinct roles in radiationinduced apoptosis in HeLa cells. Cell Signal 2010; 22: 1300-7.
43. Senkal CE, Ponnusamy S, Bielawski J, Hannun YA, Ogretmen B. Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways. FASEB J 2010; 24: 296-308.
44. Spassieva SD, Mullen TD, Townsend DM, Obeid LM. Disruption of ceramide synthesis by CerS2 downregulation leads to autophagy and the unfolded protein response. Biochem J 2009; 424: 273-83.
45. Pewzner-Jung Y, Park H, Laviad EL, Silva LC, Lahiri S, Stiban J, Erez-Roman R, Brügger B, Sachsenheimer T, Wieland F, Prieto M, Merrill AH Jr, Futerman AH. A critical role for ceramide synthase 2 in liver homeostasis: I. Alterations in lipid metabolic pathways. J Biol Chem 2010; 285: 10902-10.
46. Ben-David O, Futerman AH. The role of the ceramide acyl chain length in neurodegeneration: involvement of ceramide synthases. Neuromolecular Med 2010; wEpub ahead of printx.
47. Johnson TE, Wood WB. Genetic analysis of life-span in Caenorhabditis elegans. Proc Natl Acad Sci USA 1982; 79: 6603-7.
48. Kenyon C. The plasticity of aging: insights from long lived mutants. Cell 2005; 120: 449-60.
49. Tedesco P, Jiang J, Wang J, Jazwinski SM, Johnson TE. Genetic analysis of hyl-1, the C. elegans homolog of LAG1/LASS1. Age (Dordr) 2008; 30: 43-52.
50. Menuz V, Howell KS, Gentina S, Epstein S, Riezman I, Fornallaz-Mulhauser M, Hengartner MO, Gomez M, Riezman H, Martinou JC. Protection of C. elegans from anoxia by Hyl-2 ceramide synthase. Science 2009; 324: 381-4.
51. Cutler RG, Mattson MP. Sphingomyelin and ceramide as regulators of development and lifespan. Mech Ageing Dev 2001; 122: 895-908.
52. Jazwinski SM, Conzelmann A. LAG1 puts the focus on ceramide signaling. Int J Biochem Cell Biol 2002; 34: 1491-5.
53. Obeid LM, Hannun YA. Ceramide, stress, and a 'LAG' in aging. Sci Aging Knowledge Environ 2003; 39: PE27.
54. Stratford S, Hoehn KL, Liu F, Summers SA. Regulation of insulin action by ceramide: dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J Biol Chem 2004; 279: 36608-15.
55. Deng X, Yin X, Allan R, Lu DD, Maurer CW, Haimovitz-Friedman A, Fuks Z, Shaham S, Kolesnick R. Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science 2008; 322: 110-5.
56. Ashrafi K, Chang FY, Watts JL, Fraser AG, Kamath RS, Ahringer J, Ruvkun G. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 2003; 421: 268-72.
57. Bauer R. Towards understanding regulation of energy homeostasis by ceramide synthases. In: Meyerhof W, Beisiegel U, Joost H-G, editors. Sensory and metabolic control of energy balance. Heidelberg: Springer, 2010: in press.
58. Dobrosotskaya IY, Seegmiller AC, Brown MS, Goldstein JL, Rawson RB. Regulation of SREBP processing and membrane lipid production by phospholipids in Drosophila. Science 2002; 296: 879-83.
59. Acharya U, Acharya JK. Enzymes of sphingolipid metabolism in Drosophila melanogaster. Cell Mol Life Sci 2005; 62: 128-42.
60. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 14: 840-6.
61. Simha V, Garg A. Lipodystrophy: lessons in lipid and energy metabolis. Curr Opin Lipidol 2006; 17: 162-9.
62. Shah C, Yang G, Lee I, Bielawski J, Hannun YA, Samad F. Protection from high fat diet-induced increase in ceramide in mice lacking plasminogen activator inhibitor 1. J Biol Chem 2008; 283: 13538-48.
63. Yang G, Badeanlou L, Bielawski J, Roberts AJ, Hannun YA, Samad F. Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. Am J Physiol Endocrinol Metab 2009; 297: E211-24.
64. Unger RH. Minireview. Weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003; 144: 5159-65.
65. Holland WL, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev 2008; 29: 381-402.
66. Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, Narra K, Hoehn KL, Knotts TA, Siesky A, Nelson DH, Karathanasis SK, Fontenot GK, Birnbaum MJ, Summers SA. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 2007; 5: 167-79.
67. Gallardo N, Bonzón-Kulichenko E, Fernández-Agulló T, Moltó E, Gómez-Alonso S, Blanco P, Carrascosa JM, Ros M, Andrés A. Tissue-specific effects of central leptin on the expression of genes involved in lipid metabolism in liver and white adipose tissue. Endocrinology 2007; 148: 5604-10.
68. Worgall TS, Juliano RA, Seo T, Deckelbaum RJ. Ceramide synthesis correlates with the posttranscriptional regulation of the sterol-regulatory element-binding protein. Arterioscler Thromb Vasc Biol 2004; 24: 943-8.
69. Cohen P, Miyazaki M, Socci ND, Hagge-Greenberg A, Liedtke W, Soukas AA, Sharma R, Hudgins LC, Ntambi JM, Friedman JM. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 2002; 297: 240-3.
70. Mesika A, Ben-Dor S, Laviad EL, Futerman AH. A new functional motif in Hox domain-containing ceramide synthases: identification of a novel region flanking the Hox and TLC domains essential for activity. J Biol Chem 2007; 282: 27366-73.
71. Felsenstein J. PHYLIP (Phylogeny Inference Package) version 3.6. Distributed by the author. Department of Genome Sciences, University of Washington, Seattle, WA, USA, 2005.
72. Vallée B, Riezman H. Lip1p: a novel subunit of acyl-CoA ceramide synthase. EMBO J 2005; 24: 730-41.
73. Han MV, Zmasek CM. phyloXML: XML for evolutionary biology and comparative genomics. BMC Bioinformatics 2009; 10: 356.
74. Zmasek CM, Eddy SR. ATV: display and manipulation of annotated phylogenetic trees. Bioinformatics 2001; 17: 383-4.
75. Holland PW, Booth HA, Bruford EA. Classification and nomenclature of all human homeobox genes. BMC Biol 2007; 5: 47.
76. Bürglin TR. A comprehensive classification of homeobox genes. In: Duboule D, editor. Guidebook to the homeobox genes. Oxford: Oxford University Press, 1994: 25-71.
77. Chamberlain EM, Sanders MM. Identification of the novel player deltaEF1 in estrogen transcriptional cascades. Mol Cell Biol 1999; 19: 3600-6.
78. Vandewalle C, Comijn J, De Craene B, Vermassen P, Bruyneel E, Andersen H, Tulchinsky E, Van Roy F, Berx G. SIP1/ZEB2 induces EMT by repressing genes of different epithelial cellcell junctions. Nucleic Acids Res 2005; 33: 6566-78.
79. Hassan B, Li L, Bremer KA, Chang W, Pinsonneault J, Vaessin H. Prospero is a panneural transcription factor that modulates homeodomain protein activity. Proc Natl Acad Sci USA 1997; 94: 10991-6.
80. Petrova TV, Mäkinen T, Mäkelä TP, Saarela J, Virtanen I, Ferrell RE, Finegold DN, Kerjaschiki D, Ylä-Herttuala S, Alitalo K. Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J 2002; 21: 4593-9.
81. Nishijiama I, Ohtoshi A. Characterization of a novel prosperorelated homeobox gene, Prox2. Mol Genet Genomics 2006; 275: 471-8.
82. Iyaguchi D, Yao M, Watanabe N, Nishihira J, Tanaka I. DNA recognition mechanism of the ONECUT homeodomain of transcription factor HNF-6. Structure 2007; 15: 75-83.
83. Mandel S, Rechavi G, Gozes I. Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis. Dev Biol 2007; 303: 814-24.
84. Berger MF, Badis G, Gehrke AR, Talukder S, Philippakis AA, Peña-Castillo L, Alleyne TM, Mnaimneh S, Botvinnik OB, Chan ET, Khalid F, Zhang W, Newburger D, Jaeger SA, Morris QD, Bulyk ML, Hughes TR. Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences. Cell 2008; 133: 1266-76.
85. Kornberg TB. Minireview. Understanding the homeodomain. J Biol Chem 1993; 36: 26813-6.
86. Ruhul Momen AZM, Onuki H, Hirota H, Tomizawa T, Koshiba S, Kigawa T, Yokoyama S. Solution structure of RSGI RUH-034, a homeodomain from mouse cDNA. RIKEN Structural Genomics/Proteomics Initiative (RSGI) 2005; DOI:10.2210/ pdb2cqx/pdb.
87. Kamatari YO, Tomizawa T, Koshiba S, Inoue M, Kigawa T, Yokoyama S. Solution structure of the homeobox domain of mouse LAG1 longevity assurance homolog 6. RIKEN Structural Genomics/Proteomics Initiative (RSGI), 2005; DOI: 10.2210/pdb1x2m/pdb.
88. Gibrat JF, Madej T, Bryant SH. Surprising similarities in structure comparison. Curr Opin Struct Biol 1996; 6: 377-85.