Genome analysis of sphingolipid metabolism-related genes in Tetrahymena thermophila and identification of a fatty acid 2-hydroxylase involved in the sexual stage of conjugation.
Amino Acid Sequence
/ genetics
Conjugation, Genetic
/ genetics
Fatty Acid Desaturases
/ genetics
Fatty Acids
/ genetics
Genome, Bacterial
/ genetics
Lipid Metabolism
/ genetics
Lipids
/ genetics
Mixed Function Oxygenases
/ metabolism
Phylogeny
Sphingolipids
/ genetics
Tetrahymena thermophila
/ genetics
Tetrahymena
ciliates
conjugation
fatty acid 2-hydroxylase
hydroxy fatty acids
sphingolipid
Journal
Molecular microbiology
ISSN: 1365-2958
Titre abrégé: Mol Microbiol
Pays: England
ID NLM: 8712028
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
17
03
2020
revised:
15
07
2020
accepted:
16
07
2020
pubmed:
28
7
2020
medline:
24
8
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
Sphingolipids are bioactive lipids present in all eukaryotes. Tetrahymena thermophila is a ciliate that displays remarkable sphingolipid moieties, that is, the unusual phosphonate-linked headgroup ceramides, present in membranes. To date, no identification has been made in this organism of the functions or related genes implicated in sphingolipid metabolism. By gathering information from the T. thermophila genome database together with sphingolipid moieties and enzymatic activities reported in other Tetrahymena species, we were able to reconstruct the putative de novo sphingolipid metabolic pathway in T. thermophila. Orthologous genes of 11 enzymatic steps involved in the biosynthesis and degradation pathways were retrieved. No genes related to glycosphingolipid or phosphonosphingolipid headgroup transfer were found, suggesting that both conserved and innovative mechanisms are used in ciliate. The knockout of gene TTHERM_00463850 allowed to identify the gene encoding a putative fatty acid 2-hydroxylase, which is involved in the biosynthesis pathway. Knockout cells have shown several impairments in the sexual stage of conjugation since different mating types of knockout strains failed to form cell pairs and complete the conjugation process. This fatty acid 2-hydroxylase gene is the first gene of a sphingolipid metabolic pathway to be identified in ciliates and have a critical role in their sexual stage.
Substances chimiques
Fatty Acids
0
Lipids
0
Sphingolipids
0
Mixed Function Oxygenases
EC 1.-
Fatty Acid Desaturases
EC 1.14.19.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
775-788Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
Acharya, U. and Acharya, J.K. (2005) Enzymes of Sphingolipid metabolism in Drosophila melanogaster. CMLS Cellular and Molecular Life Sciences, 62(2), 128-142.
Blackburn, E.H. and Gall, J.G. (1978) A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. Journal of Molecular Biology, 120(1), 33-53.
Bligh, E.G. and Dyer, W.J. (1959) A rapid method of total lipid extraction and purification. Canadian Journal of Biochemistry and Physiology, 37(1), 911-917.
Bosson, R. (2006) GUP1 of Saccharomyces cerevisiae encodes an O-acyltransferase involved in remodeling of the GPI Anchor. Molecular Biology of the Cell, 17(6), 2636-2645.
Cassidy-Hanley, D., Bowen, J., Lee, J.H., Cole, E., VerPlank, L.A., Gaertig, J., et al. (1997) Germline and somatic transformation of mating Tetrahymena thermophila by particle bombardment. Genetics, 146(1), 135-147.
Cassidy-Hanley, D.M. (2012) Tetrahymena in the laboratory: strain resources, methods for culture, maintenance, and storage. Methods in Cell Biology, 109, 237-276.
Chalker, D.L. (2012) Transformation and strain engineering of Tetrahymena. Methods in Cell Biology, 109, 327-345.
Cole, E. and Sugai, T. (2012) Developmental progression of Tetrahymena through the cell cycle and conjugation. Methods in Cell Biology, 109, 177-236.
Cole, E. S. (2016) Cell-cell interactions leading to establishment of a mating junction in Tetrahymena and Paramecium, two “contact-mediated” mating systems. G, Witzany & M, Nowacki, In Biocommunication of ciliates (pp. 195-220). Cham: Springer International Publishing.
Darriba, Diego, et al. (2011) ProtTest 3: fast selection of best-fit models of protein evolution. Bioinformatics, 27(8), 1164-1165.
Eckhardt, M., Yaghootfam, A., Fewou, S.N., Zöller, I. and Gieselmann, V. (2005) A mammalian fatty acid hydroxylase responsible for the formation of α-hydroxylated galactosylceramide in myelin. Biochemical Journal, 388(1), 245-254.
Edvardson, S., Hama, H., Shaag, A., Gomori, J.M., Berger, I., Soffer, D., et al. (2008) Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. American Journal of Human Genetics, 83(5), 643-648.
Eisen, J., Coyne, R., Wu, M. and Wu, D. (2006) Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLoS Biology, 4(9), e286.
Elguero, M.E., Nudel, C.B. and Nusblat, A.D. (2018) Biotechnology in ciliates: an overview. Critical Reviews in Biotechnology, 39(2), 220-234.
Elliott, A.M. and Hayes, R.E. (1953) Mating types in tetrahymena. The Biological Bulletin, 105(2), 269-284.
Forte, M., Satow, Y., Nelson, D. and Kung, C. (1981) Mutational alteration of membrane phospholipid composition and voltage-sensitive ion channel function in paramecium. Proceedings of the National Academy of Sciences of the United States of America, 78(11), 7195-7199.
Gault, C.R., Obeid, L.M. and Hannun, Y.A. (2010). An overview of sphingolipid metabolism: from synthesis to breakdown. Advances in Experimental Medicine and Biology, 688, 1-23.
Greider, C.W. and Blackburn, E.H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell, 43(2), 405-413.
Guindon, S., Dufayard, J.F., Lefort, V., Anisimova, M., Hordijk, W. and Gascuel, O. (2010) New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Systematic Biology, 59(3), 307-321.
Guo, L., Zhou, D., Pryse, K.M., Okunaded, A.L. and Su, X. (2010) Fatty acid 2-hydroxylase mediates diffusional mobility of raft-associated lipids, GLUT4 level, and lipogenesis in 3T3-L1 adipocytes. Journal of Biological Chemistry, 285(33), 25438-25447.
Haak, D., Gable, K., Beeler, T. and Dunn, T. (1997) Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p. The Journal of Biological Chemistry, 272(47), 29704-29710.
Hama, H. (2010) Fatty acid 2-Hydroxylation in mammalian sphingolipid biology. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1801(4), 405-414.
Hamilton, E.P. and Orias, E. (2000) Genetic crosses: setting up crosses, testing progeny, and isolating phenotypic assortants. Methods in Cell Biology, 62, 219-228.
Hanahan, D.J. (1997) A Guide to Phospholipid Chemistry, 76, 3rd edition. Washington, DC: Oxford University Press, pp. 1-326.
Hannun, Y.A. and Obeid, L.M. (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nature Reviews Molecular Cell Biology, 9(2), 139-150.
Hannun, Y.A. and Obeid, L.M. (2017) Sphingolipids and their metabolism in physiology and disease. Nature Reviews Molecular Cell Biology, 19(3), 175-191.
He, D., Fiz-Palacios, O., Fu, C.J., Tsai, C.C. and Baldauf, S.L. (2014) An alternative root for the eukaryote tree of life. Current Biology, 24(4), 465-470.
Hung, C.Y., Ko, Y.G. and Thompson, G.A. (1995) Temperature-induced alteration of inositolphosphorylceramides in the putative glycosylated lipid precursors of Tetrahymena mimbres glycosylphosphatidylinositol-anchored proteins. The Biochemical Journal, 307(1), 107-113.
Ikushiro, H., Hayashi, H. and Kagamiyama, H. (2001) A water-soluble homodimeric serine palmitoyltransferase from Sphingomonas paucimobilis EY2395T strain purification, characterization, cloning, and overproduction. Journal of Biological Chemistry, 276(21), 18249-18256.
Jin, Q., Ren, Y., Wang, M., Suraneni, P.K., Li, D., Crispino, J.D., et al. (2016) Novel function of FAXDC2 in megakaryopoiesis. Blood Cancer Journal, 6(9), e478.
Kaneshiro, E.S. (1987) Lipids of Paramecium. Journal of Lipid Research, 28(11), 1241-1258.
Kaneshiro, E.S., Jayasimhulu, K., Sul, D. and Erwin, J.A. (1997) Identification and initial characterizations of free, glycosylated, and phosphorylated ceramides of Paramecium. Journal of Lipid Research, 38(12), 2399-2410.
Kataoka, K., Schoeberl, U.E. and Mochizuki, K. (2010) Modules for C-terminal epitope tagging of Tetrahymena genes. Journal of Microbiological Methods, 82, 342-346.
Kaya, K., Ramesha, C.S. and Thompson, G.A. (1984a) Temperature-induced changes in the hydroxy and non-hydroxy fatty-acid containing sphingolipids abundant in the surface-membrane of tetrahymena-pyriformis nt-1. Journal of Lipid Research, 25(1), 68-74.
Kaya, K., Ramesha, C.S. and Thompson, G.A. (1984b) On the formation of alpha-hydroxy fatty acids. Evidence for a direct hydroxylation of nonhydroxy fatty acid-containing sphingolipids. The Journal of Biological Chemistry, 259(6), 3548-3553.
Kota, V. and Hama, H. (2014) 2’-Hydroxy ceramide in membrane homeostasis and cell signaling. Advances in Biological Regulation, 54(1), 223-230.
Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E. and Cech, T.R. (1982) Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena. Cell, 31(1), 147-157.
Kurczy, M.E., Piehowski, P.D., Van Bell, C.T., Heien, M.L., Winograd, N. and Ewing, A.G. (2010) Mass spectrometry imaging of mating Tetrahymena show that changes in cell morphology regulate lipid domain formation. Proceedings of the National Academy of Sciences of the United States of America, 107(7), 2751-2756.
Leondaritis, G., Sarri, T., Dafnis, I., Efstathiou, A. and Galanopoulou, D. (2011) Biochemical and genetic evidence for the presence of multiple phosphatidylinositol- and phosphatidylinositol 4,5-bisphosphate-specific phospholipases C in Tetrahymena. Eukaryotic Cell, 10(3), 412-422.
Li, Y., Wang, C., Huang, Y., Fu, R., Zheng, H., Zhu, Y., et al. (2018) C. elegans fatty acid two-hydroxylase regulates intestinal homeostasis by affecting heptadecenoic acid production. Cellular Physiology and Biochemistry, 49(3), 947-960.
Martindale, D.W., Allis, C.D. and Bruns, P.J. (1982) Conjugation in Tetrahymena thermophila. A temporal analysis of cytological stages. Experimental Cell Research, 140(1), 227-236.
Merrill, A.H. (2011) Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chemical Reviews, 111(10), 6387-6422.
Michaelson, L.V., Napier, J.A., Molino, D. and Faure, J.-D. (2016) Plant sphingolipids: their importance in cellular organization and adaption. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1861(9), 1329-1335.
Mina, J.G., Thye, J.K., Alqaisi, A.Q.I., Bird, L.E., Dods, R.H., Grøftehauge, M.K., et al. (2017) Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites. Journal of Biological Chemistry, 292(29), 12208-12209.
Mochizuki, K., Fine, N.A., Fujisawa, T. and Gorovsky, M.A. (2002) Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena. Cell, 110(6), 689-699.
Mochizuki, K. and Gorovsky, M.A. (2004) Conjugation-specific small RNAs in Tetrahymena have predicted properties of scan (scn) RNAs involved in genome rearrangement. Genes and Development, 18(17), 2068-2073.
Montefusco, D.J., Matmati, N. and Hannun, Y.A. (2014) The yeast sphingolipid signaling landscape. Chemistry and Physics of Lipids, 177, 26-40.
Nagano, M., Takahara, K., Fujimoto, M., Tsutsumi, N., Uchimiya, H. and Kawai-Yamada, M. (2012) Arabidopsis sphingolipid fatty acid 2-hydroxylases (AtFAH1 and AtFAH2) are functionally differentiated in fatty acid 2-hydroxylation and stress responses. Plant Physiology, 159(3), 1138-1148.
Natter, K., Leitner, P., Faschinger, A., Wolinski, H., McCraith, S., Fields, S., et al. (2005) The spatial organization of lipid synthesis in the yeast Saccharomyces cerevisiae derived from large scale green fluorescent protein tagging and high resolution microscopy. Molecular & Cellular Proteomics, 4(5), 662-672.
Nishizuka, Y. (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science (New York, N.Y.), 258(5082), 607-614.
Nozawa, Y. and Thompson, G. A. (1971) Studies of membrane formation in Tetrahymena pyriformis. II. Isolation and lipid analysis of cell fractions. The Journal of Cell Biology, 43(3), 712-721.
Nusblat, A.D., Bright, L.J. and Turkewitz, A.P. (2012) Conservation and innovation in Tetrahymena membrane traffic: proteins, lipids, and compartments. Methods in Cell Biology, 109, 141-175.
Nusblat, A.D., Najle, S.R., Tomazic, M.L., Uttaro, A.D. and Nudel, C.B. (2009) C-5(6) sterol desaturase from Tetrahymena thermophila: gene identification and knockout, sequence analysis, and comparison to other C-5(6) sterol desaturases. Eukaryotic Cell.
Olsen, I. and Jantzen, E. (2001) Sphingolipids in bacteria and fungi. Anaerobe, 7(2), 103-112.
Ostrowski, S.G., Bell, C.T.V., Winograd, N. and Ewing, A.G. (2004) Mass spectrometric imaging of highly curved membranes during Tetrahymena mating. Science, 35(5680), 71-73.
Poklepovich, T.J., Rinaldi, M.A., Tomazic, M.L., Favale, N.O., Turkewitz, A.P., Nudel, C.B., et al. (2012) The cytochrome b5 dependent C-5(6) sterol desaturase DES5A from the endoplasmic reticulum of Tetrahymena thermophila complements ergosterol biosynthesis mutants in Saccharomyces cerevisiae. Steroids, 77(13), 1313-1320.
Potter, K.A., Kern, M.J., Fullbright, G., Bielawski, J., Scherer, S.S., Yum, S.W., et al. (2011) Central nervous system dysfunction in a mouse model of Fa2H deficiency. Glia, 59(7), 1009-1021.
Pratt, S., Wansadhipathi-Kannangara, N.K., Bruce, C.R., Mina, J.G., Shams-Eldin, H., Casas, J., et al. (2013) Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii. Molecular and Biochemical Parasitology, 187(1), 43-51.
Ramakrishnan, S., Serricchio, M., Striepen, B. and Bütikofer, P. (2013) Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans. Progress in Lipid Research, 52(4), 488-512.
Ruehle, M.D., Orias, E. and Pearson, C.G. (2016) Tetrahymena as a unicellular model eukaryote: genetic and genomic tools. Genetics, 203(2), 649-665.
Serhan, C.N. and Savill, J. (2005) Resolution of inflammation: the beginning programs the end. Nature Immunology, 6(12), 1191-1197.
Shang, Y., Song, X., Bowen, J., Corstanje, R., Gao, Y., Gaertig, J., et al. (2002) A robust inducible-repressible promoter greatly facilitates gene knockouts, conditional expression, and overexpression of homologous and heterologous genes in Tetrahymena thermophila. Proceedings of the National Academy of Sciences of the United States of America, 99, 3734-3739.
Shanklin, J., Whittle, E. and Fox, B.G. (1994) Eight histidine residues are catalytically essential in a membrane-associated iron enzyme, stearoyl-CoA desaturase, and are conserved in alkane hydroxylase and xylene monooxygenase. Biochemistry, 33(43), 12787-12794.
Simons, K. and Ikonen, E. (1997) Functional rafts in cell membranes. Nature, 387(6633), 569-572.
Smith, T.K. and Bütikofer, P. (2010) Lipid metabolism in Trypanosoma brucei. Molecular and Biochemical Parasitology, 172(2), 66-79.
Sugita, M., Fukunaga, Y., Ohkawa, K., Nozawa, Y. and Hori, T. (1979) Structural components of sphingophosphonolipids from the ciliated protozoan, Tetrahymena pyriformis WH-14. The Journal of Biochemistry, 86(2), 281-288.
Tafesse, F.G., Ternes, P. and Holthuis, J.C.M. (2006) The multigenic sphingomyelin synthase family. The Journal of Biological Chemistry, 281(40), 29421-29425.
Taketomi, T. (1961) Phospholipids in Tetrahymena pyriformis W. Zeitschrift für allgemeine Mikrobiologie, 1(5), 331-340.
Taverna, S.D., Coyne, R.S. and Allis, C.D. (2002) Methylation of histone H3 at lysine 9 targets programmed DNA elimination in Tetrahymena. Cell, 110(6), 701-711.
Thompson, G.A. (1967) Studies of membrane formation in Tetrahymena pyriformis. I. Rates of phospholipid biosynthesis. Biochemistry, 6(7), 2015-2022.
Tomazic, M.L., Najle, S.R., Nusblat, A.D., Uttaro, A.D. and Nudel, C.B. (2011) A novel sterol desaturase-like protein promoting dealkylation of phytosterols in Tetrahymena thermophila. Eukaryotic Cell, 10(3), 423-434.
Tomazic, M.L., Poklepovich, T.J., Nudel, C.B. and Nusblat, A.D. (2014) Incomplete sterols and hopanoids pathways in ciliates: gene loss and acquisition during evolution as a source of biosynthetic genes. Molecular Phylogenetics and Evolution, 74, 122-134.
Uchida, Y., Hama, H., Alderson, N.L., Douangpanya, S., Wang, Y., Crumrine, D.A., et al. (2007) Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation. Journal of Biological Chemistry, 282(18), 13211-13219.
Villasmil, M.L., Gallo-Ebert, C., Liu, H.Y., Francisco, J. and Nickels, J.T. (2017) A link between very long chain fatty acid elongation and mating-specific yeast cell cycle arrest. Cell Cycle, 16(22), 2192-2203.
Viswanathan, C.V. and Rosenberg, H. (1973) Isolation of ceramide-monomethylaminoethylphosphonate from the lipids of Tetrahymena pyriformis W. Journal of Lipid Research, 14(3), 327-330.
Wang, S., Banno, Y. and Nozawa, Y. (2002) Two forms of membrane-bound sphingosine kinase in Tetrahymena and activity changes during growth and the cell cycle. The Journal of Eukaryotic Microbiology, 49(4), 305-311.
Xiong, J., Wang, G., Cheng, J., Tian, M., Pan, X., Warren, A., et al. (2015) Genome of the facultative scuticociliatosis pathogen Pseudocohnilembus persalinus provides insight into its virulence through horizontal gene transfer. Scientific Reports, 5(1), 15470.
Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J. and Zhang, Y. (2015) The I-TASSER Suite: protein structure and function prediction. Nature Methods, 12(1), 7-8.
Yao, Y., Yang, X., Sun, L., Sun, S., Huang, X., Zhou, D., et al. (2019) Fatty acid 2-hydroxylation inhibits tumor growth and increases sensitivity to cisplatin in gastric cancer. EBioMedicine, 41, 267.
Zhang, K. and Beverley, S.M. (2010) Phospholipid and sphingolipid metabolism in Leishmania. Molecular and Biochemical Parasitology, 170(2), 55-64.
Zhu, G., Koszelak-Rosenblum, M., Connelly, S.M., Dumont, M.E. and Malkowski, M.G. (2015) The crystal structure of an integral membrane fatty acid α-hydroxylase. The Journal of Biological Chemistry, 290(50), 29820-29833.