Publications

• Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p.

  Haak D., Gable K., Beeler T., Dunn T.

  The Saccharomyces cerevisiae SCS7 and SUR2 genes are members of a gene family that encodes enzymes that desaturate or hydroxylate lipids. Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty aci ... >> More

  The Saccharomyces cerevisiae SCS7 and SUR2 genes are members of a gene family that encodes enzymes that desaturate or hydroxylate lipids. Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide, and Scs7p is required for the hydroxylation of the very long chain fatty acid. Neither SCS7 nor SUR2 are essential for growth, and lack of the Scs7p- or Sur2p-dependent hydroxylation does not prevent the synthesis of mannosyldiinositolphosphorylceramide, the mature sphingolipid found in yeast. Deletion of either gene suppresses the Ca2+-sensitive phenotype of csg2Delta mutants, which arises from overaccumulation of inositolphosphorylceramide due to a defect in sphingolipid mannosylation. Characterization of scs7 and sur2 mutants is expected to provide insight into the function of ceramide hydroxylation. << Less

  J. Biol. Chem. 272:29704-29710(1997) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae.

  Grilley M.M., Stock S.D., Dickson R.C., Lester R.L., Takemoto J.Y.

  The Saccharomyces cerevisiae gene SYR2, necessary for growth inhibition by the cyclic lipodepsipeptide syringomycin E, is shown to be required for 4-hydroxylation of long chain bases in sphingolipid biosynthesis. Four lines of support for this conclusion are presented: (a) the predicted Syr2p show ... >> More

  The Saccharomyces cerevisiae gene SYR2, necessary for growth inhibition by the cyclic lipodepsipeptide syringomycin E, is shown to be required for 4-hydroxylation of long chain bases in sphingolipid biosynthesis. Four lines of support for this conclusion are presented: (a) the predicted Syr2p shows sequence similarity to diiron-binding membrane enzymes involved in oxygen-dependent modifications of hydrocarbon substrates, (b) yeast strains carrying a disrupted SYR2 allele produced sphingoid long chain bases lacking the 4-hydroxyl group present in wild type strains, (c) 4-hydroxylase activity was increased in microsomes prepared from a SYR2 overexpression strain, and (d) the syringomycin E resistance phenotype of a syr2 mutant strain was suppressed when grown under conditions in which exogenous 4-hydroxysphingoid long chain bases were incorporated into sphingolipids. The syr2 strain produced wild type levels of sphingolipids, substantial levels of hydroxylated very long chain fatty acids, and the full complement of normal yeast sphingolipid head groups. These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases, that this hydroxylation is not essential for growth, and that the 4-hydroxyl group of sphingolipids is necessary for syringomycin E action on yeast. << Less

  J. Biol. Chem. 273:11062-11068(1998) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation.

  Mizutani Y., Kihara A., Igarashi Y.

  The C4-hydroxylation of dihydrosphingosine or dihydroceramide is a key reaction in the biosynthesis of phytosphingolipids, both in yeasts and in mammalian cells. Mouse DES2 (mDES2) was recently cloned and shown to work as a Delta4-desaturase/C4-hydroxylase, when expressed in yeast cells. Here, we ... >> More

  The C4-hydroxylation of dihydrosphingosine or dihydroceramide is a key reaction in the biosynthesis of phytosphingolipids, both in yeasts and in mammalian cells. Mouse DES2 (mDES2) was recently cloned and shown to work as a Delta4-desaturase/C4-hydroxylase, when expressed in yeast cells. Here, we cloned a human homologue of mDES2, hDES2, by homology search utilizing a BLAST program. When expressed in HEK 293 cells, hDES2 exhibited hydroxylase activity for dihydroceramide. Northern blot analyses of hDES2 revealed high expression in skin, intestines, and kidney, sites reportedly possessing high levels of phytosphingolipids. Furthermore, up-regulation of hDES2 mRNA expression and subsequent phytoceramide production were observed during vitamin C/serum-induced differentiation of human keratinocytes. These results suggest that the newly cloned hDES2 plays an essential role in phytosphingolipid synthesis in human skin and other phytosphingolipid-containing tissues. << Less

  FEBS Lett. 563:93-97(2004) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Sphingolipid functions in Saccharomyces cerevisiae.

  Dickson R.C., Lester R.L.

  Recent advances in understanding sphingolipid metabolism and function in Saccharomyces cerevisiae have moved the field from an embryonic, descriptive phase to one more focused on molecular mechanisms. One advance that has aided many experiments has been the uncovering of genes for the biosynthesis ... >> More

  Recent advances in understanding sphingolipid metabolism and function in Saccharomyces cerevisiae have moved the field from an embryonic, descriptive phase to one more focused on molecular mechanisms. One advance that has aided many experiments has been the uncovering of genes for the biosynthesis and breakdown of sphingolipids. S. cerevisiae seems on the verge of becoming the first organism in which all sphingolipid metabolic genes are identified. Other advances include the demonstration that S. cerevisiae cells have lipid rafts composed of sphingolipids and ergosterol and that specific proteins associate with rafts. Roles for phytosphingosine (PHS) and dihydrosphingosine (DHS) in heat stress continue to be uncovered including regulation of the transient cell cycle arrest, control of putative signaling pathways that govern cell integrity, endocytosis, movement of the cortical actin cytoskeleton and regulation of protein breakdown in the plasma membrane. Other studies suggest roles for sphingolipids in exocytosis, growth regulation and longevity. Finally, some progress has been made in understanding how sphingolipid synthesis is regulated and how sphingolipid levels are maintained. << Less

  Biochim Biophys Acta 1583:13-25(2002) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Identification and characterization of a sphingolipid delta 4-desaturase family.

  Ternes P., Franke S., Zaehringer U., Sperling P., Heinz E.

  Sphingolipids desaturated at the Delta4-position are important signaling molecules in many eukaryotic organisms, including mammals. In a bioinformatics approach, we now identified a new family of protein sequences from animals, plants, and fungi and characterized these sequences biochemically by e ... >> More

  Sphingolipids desaturated at the Delta4-position are important signaling molecules in many eukaryotic organisms, including mammals. In a bioinformatics approach, we now identified a new family of protein sequences from animals, plants, and fungi and characterized these sequences biochemically by expression in Saccharomyces cerevisiae. This resulted in the identification of the enzyme sphingolipid Delta4-desaturase (dihydroceramide desaturase) from Homo sapiens, Mus musculus, Drosophila melanogaster, and Candida albicans, in addition to a bifunctional sphingolipid Delta4-desaturase/C-4-hydroxylase from M. musculus. Among the sequences investigated are the Homo sapiens membrane lipid desaturase, the M. musculus degenerative spermatocyte, and the Drosophila melanogaster degenerative spermatocyte proteins. During spermatogenesis, but not oogenesis of des mutant flies, both cell cycle and spermatid differentiation are specifically blocked at the entry into the first meiotic division, leading to male sterility. This mutant phenotype can be restored to wild-type by complementation with a functional copy of the des gene (Endo, K., Akiyama, T., Kobayashi S., and Okada, M. (1996) Mol. Gen. Genet. 253, 157-165). These results suggest that Delta4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during Drosophila spermatogenesis. << Less

  J. Biol. Chem. 277:25512-25518(2002) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Functional characterization of sphingolipid C4-hydroxylase genes from Arabidopsis thaliana.

  Sperling P., Ternes P., Moll H., Franke S., Zaehringer U., Heinz E.

  In the genome of Arabidopsis thaliana, two genes were identified encoding isoenzymes for C4-hydroxylation of long chain bases (LCB) in plant sphingolipids. Both predicted proteins consist of 258 amino acid residues (77% identity) which show sequence similarity to di-iron-binding enzymes, such as S ... >> More

  In the genome of Arabidopsis thaliana, two genes were identified encoding isoenzymes for C4-hydroxylation of long chain bases (LCB) in plant sphingolipids. Both predicted proteins consist of 258 amino acid residues (77% identity) which show sequence similarity to di-iron-binding enzymes, such as Sur2p and Erg3p from yeast, involved in oxygen-dependent lipid modifications. Heterologous expression of these genes in a yeast sur2Delta-null mutant lacking C4-LCB hydroxylation resulted in the formation of D-ribo-C(18)- and -C(20)-phytosphinganine. The identity and stereochemical configuration of the isolated trihydroxybases was confirmed by electrospray ionization-mass spectroscopy, gas-liquid chromatography-mass spectrometry and 1H-nuclear magnetic resonance spectroscopy. These results represent the first functional identification of SUR2 genes from plants as well as from any organism other than yeast. << Less

  FEBS Lett. 494:90-94(2001) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.