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PDR16 and PDR17, two homologous genes of Saccharomyces cerevisiae, affect lipid biosynthesis and resistance to multiple drugs.

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van den Hazel, Bart H. [UCL] Pichler, Harald do Valle Matta, Maria Adelaide Leitner, Erich Goffeau, André [UCL] Daum, Günther

The Saccharomyces cerevisiae open reading frame YNL231C was recently found to be controlled by the multiple drug resistance regulator Pdr1p. Here we characterize YNL231C (PDR16) and its homologue YNL264C (PDR17). Deletion of PDR16 resulted in hypersensitivity of yeast to azole inhibitors of ergosterol biosynthesis. While no increase in drug sensitivity was found upon deletion of PDR17 alone, a Deltapdr16,Deltapdr17 double mutant was hypersensitive to a broad range of drugs. Both mutations caused significant changes of the lipid composition of plasma membrane and total cell extracts. Deletion of PDR16 had pronounced effects on the sterol composition, whereas PDR17 deletion mainly affected the phospholipid composition. Thus, Pdr16p and Pdr17p may regulate yeast lipid synthesis like their distant homologue, Sec14p. The azole sensitivity of the PDR16-deleted strain may be the result of imbalanced ergosterol synthesis. Impaired plasma membrane barrier function resulting from a change in the lipid composition appears to cause the increased drug sensitivity of the double mutant strain Deltapdr16,Deltapdr17. The uptake rate of rhodamine-6-G into de-energized cells was shown to be almost 2-fold increased in a Deltapdr16,Deltapdr17 strain as compared with wild-type and Deltapdr5 strains. Collectively, our results indicate that PDR16 and PDR17 control levels of various lipids in various compartments of the cell and thereby provide a mechanism for multidrug resistance unrecognized so far.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 1999
Journal information "The Journal of biological chemistry" - Vol. 274, no. 4, p. 1934-41 (1999)
Peer reviewed yes
issn 0021-9258
Publication status Publié
Affiliation UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject Base Sequence ; Cell Membrane - metabolism ; DNA Primers ; Drug Resistance, Multiple - genetics ; Gene Deletion ; Genes, Fungal ; Membrane Lipids - biosynthesis ; Saccharomyces cerevisiae - genetics - metabolism
Links
  1. Bankaitis Vytas A., Aitken Jacqueline R., Cleves Ann E., Dowhan William, An essential role for a phospholipid transfer protein in yeast Golgi function, 10.1038/347561a0
  2. Balzi Elisabetta, Goffeau André, Genetics and biochemistry of yeast multidrug resistance, 10.1016/0005-2728(94)90102-3
  3. Skinner H. B., McGee T. P., McMaster C. R., Fry M. R., Bell R. M., Bankaitis V. A., The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity., 10.1073/pnas.92.1.112
  4. Kearns Brian G., McGee Todd P., Mayinger Peter, Gedvilaite Alma, Phillips Scott E., Kagiwada Satoshi, Bankaitis Vytas A., Essential role for diacylglycerol in protein transport from the yeast Golgi complex, 10.1038/387101a0
  5. Patton-Vogt Jana L., Griac Peter, Sreenivas Avula, Bruno Vincent, Dowd Susan, Swede Marci J., Henry Susan A., Role of the Yeast Phosphatidylinositol/Phosphatidylcholine Transfer Protein (Sec14p) in Phosphatidylcholine Turnover andINO1Regulation, 10.1074/jbc.272.33.20873
  6. Cunningham E., Tan S. K., Swigart P., Hsuan J., Bankaitis V., Cockcroft S., The yeast and mammalian isoforms of phosphatidylinositol transfer protein can all restore phospholipase C-mediated inositol lipid signaling in cytosol-depleted RBL-2H3 and HL-60 cells., 10.1073/pnas.93.13.6589
  7. Cockcroft S., Ball A., Fensome A., Hara S., Jones D., Prosser S., Swigart P., Phosphatidylinositol transfer proteins: an essential requirement in inositol lipid signalling, 10.1042/bst0251125
  8. Cockcroft Shamshad, Phosphatidylinositol transfer proteins: requirements in phospholipase C signaling and in regulated exocytosis, 10.1016/s0014-5793(97)00414-6
  9. Sambrook J. Fritsch E. F. Maniatis T. (1989) Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY), 2nd Ed.
  10. Decottignies Anabelle, Grant Althea M., Nichols J. Wylie, de Wet Heidi, McIntosh David B., Goffeau André, ATPase and Multidrug Transport Activities of the Overexpressed Yeast ABC Protein Yor1p, 10.1074/jbc.273.20.12612
  11. Thierry Agnès, Fairhead Cécile, Dujon Bernard, The complete sequence of the 8·2 kb segment left ofMAT on chromosome III reveals five ORFs, including a gene for a yeast ribokinase, 10.1002/yea.320060609
  12. Balzi Elisabetta, Goffeau André, Yeast multidrug resistance: The PDR network, 10.1007/bf02110333
  13. Kolaczkowski Marcin, Michel van der Rest, Cybularz-Kolaczkowska Anna, Soumillion Jean-Philippe, Konings Wil N., André Goffeau, Anticancer Drugs, Ionophoric Peptides, and Steroids as Substrates of the Yeast Multidrug Transporter Pdr5p, 10.1074/jbc.271.49.31543
  14. Katzmann D J, Hallstrom T C, Voet M, Wysock W, Golin J, Volckaert G, Moye-Rowley W S, Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae., 10.1128/mcb.15.12.6875
  15. Alani E., Cao L., Kleckner N., A Method for Gene Disruption That Allows Repeated Use of URA3 Selection in the Construction of Multiply Disrupted Yeast Strains, 10.1534/genetics.112.541.test
  16. Winston Fred, Chumley Forrest, Fink Gerald R., [13] Eviction and transplacement of mutant genes in yeast, Recombinant DNA Part C (1983) ISBN:9780121820015 p.211-228, 10.1016/0076-6879(83)01016-2
  17. Sikorski, Genetics, 122, 19 (1989)
  18. Christianson Thomas W., Sikorski Robert S., Dante Michael, Shero James H., Hieter Philip, Multifunctional yeast high-copy-number shuttle vectors, 10.1016/0378-1119(92)90454-w
  19. CHEN E, KUANG W, LEE A, Overview of manual and automated DNA sequencing by the dideoxy chain termination method, 10.1016/s1046-2023(05)80158-6
  20. Rank G. H., Gerlach J. H., Robertson A. J., Some physiological alterations associated with pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae, 10.1007/bf00341726
  21. Serrano Ramón, [40] H+-ATPase from plasma membranes of Saccharomyces cerevisiae and Avena sativa roots: Purification and reconstitution, Methods in Enzymology (1988) ISBN:9780121820589 p.533-544, 10.1016/0076-6879(88)57102-1
  22. Daum, J. Biol. Chem., 257, 13028 (1982)
  23. Zinser Erwin, Daum Günther, Isolation and biochemical characterization of organelles from the yeast,Saccharomyces cerevisiae, 10.1002/yea.320110602
  24. Balzi, J. Biol. Chem., 262, 16871 (1987)
  25. Lowry, J. Biol. Chem., 193, 265 (1951)
  26. LAEMMLI U. K., Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4, 10.1038/227680a0
  27. Haid Albert, Suissa Mordechai, [13] Immunochemical identification of membrane proteins after sodium dodecyl sulfate—polyacrylamide gel electrophoresis, Methods in Enzymology (1983) ISBN:9780121819965 p.192-205, 10.1016/s0076-6879(83)96017-2
  28. Folch, J. Biol. Chem., 226, 497 (1957)
  29. Broekhuyse, Biochim. Biophys. Acta, 260, 449 (1968)
  30. Leber Regina, Zinser Erwin, Paltauf Fritz, Daum Gûnther, Zellnig Gûnther, Characterization of lipid particles of the yeast,Saccharomyces cerevisiae, 10.1002/yea.320101105
  31. Lewis Thomas A., Rodriguez Russell J., Parks Leo W., Relationship between intracellular sterol content and sterol esterification and hydrolysis in Saccharomyces cerevisiae, 10.1016/0005-2760(87)90020-8
  32. Nes W.David, Xu Sihua, Haddon William F., Evidence for similarities and differences in the biosynthesis of fungal sterols, 10.1016/0039-128x(89)90030-5
  33. Xu Sihua, Norton Robert A., Crumley Ferrast G., Nes W.David, Comparison of the chromatographic properties of sterols, select additional steroids and triterpenoids: gravity-flow column liquid chromatography, thin-layer chromatography, gas—liquid chromatography and high-performance liquid chromatography, 10.1016/s0021-9673(01)81462-x
  34. Delaveau Thierry, Delahodde Agn�s, Carvajal Elvira, Subik Julius, Jacq Claude, PDR3, a new yeast regulatory gene, is homologous toPDR1 and controls the multidrug resistance phenomenon, 10.1007/bf00583901
  35. Patterson Glenn W., Relation between structure and retention time of sterols in gas chromatograpphy, 10.1021/ac60304a015
  36. Ceolotto Christian, Flekl Waltraud, Schorsch Frida J., Tahotna Dana, Hapala Ivan, Hrastnik Claudia, Paltauf Fritz, Daum Günther, Characterization of a non-specific lipid transfer protein associated with the peroxisomal membrane of the yeast, Saccharomyces cerevisiae, 10.1016/s0005-2736(96)00147-2
  37. Kremer J. M. H., Van der Esker M. W., Pathmamanoharan C., Wiersema P. H., Vesicles of variable diameter prepared by a modified injection method, 10.1021/bi00636a033
  38. Somerharju Pentti J., Van Loon Douwe, Wirtz Karel W. A., Determination of the acyl chain specificity of the bovine liver phosphatidylcholine transfer protein. Application of pyrene-labeled phosphatidylcholine species, 10.1021/bi00396a048
  39. Hermetter Albin, Stütz Herbert, Franzmair Rudolf, Paltauf Fritz, 1-O-Trityl-sn-glycero-3-phosphocholine: a new intermediate for the facile preparation of mixed-acid 1,2-diacylglycerophosphocholines, 10.1016/0009-3084(89)90026-1
  40. Somerharju Pentti, Wirtz Karel W.A., Semisynthesis and properties of a fluorescent phosphatidyl-inositol analogue containing a cis-parinaroyl moiety, 10.1016/0009-3084(82)90009-3
  41. Comfurius, J. Lipid Res., 31, 1719 (1990)
  42. Higgins Joan A., Pigott Christine A., Asymmetric distribution of phosphatidylethanolamine in the endoplasmic reticulum demonstrated using trinitrobenzenesulphonic acid as a probe, 10.1016/0005-2736(82)90481-3
  43. Sperka-Gottlieb Constanze D.M., Hermetter Albin, Paltauf Fritz, Daum Guenther, Lipid topology and physical properties of the outer mitochondrial membrane of the yeast, Saccharomyces cerevisiae, 10.1016/0005-2736(88)90397-5
  44. Decottignies, J. Biol. Chem., 269, 12797 (1994)
  45. Kolaczkowski, M., Kolaczkowska, A., Luczynski, J., Witek, S., and Goffeau, A. (1998) Microbial Drug Resistance, in press.
  46. Carvajal E., Molecular and phenotypic characterization of yeast PDR1 mutants that show hyperactive transcription of various ABC multidrug transporter genes, 10.1007/s004380050584
  47. Barrett-Bee, Acta Biochim. Pol., 42, 465 (1995)
  48. Zinser E, Paltauf F, Daum G, Sterol composition of yeast organelle membranes and subcellular distribution of enzymes involved in sterol metabolism., 10.1128/jb.175.10.2853-2858.1993
  49. Wolfger Hubert, Mahé Yannick, Parle-McDermott Anne, Delahodde Agnés, Kuchler Karl, The yeast ATP binding cassette (ABC) protein genesPDR10andPDR15are novel targets for the Pdr1 and Pdr3 transcriptional regulators, 10.1016/s0014-5793(97)01382-3
  50. Kean Leslie S., Grant Althea M., Angeletti Cesar, Mahé Yannick, Kuchler Karl, Fuller Robert S., Nichols J. Wylie, Plasma Membrane Translocation of Fluorescent-labeled Phosphatidylethanolamine Is Controlled by Transcription Regulators,PDR1andPDR3, 10.1083/jcb.138.2.255
  51. McGee T. P., A phosphatidylinositol transfer protein controls the phosphatidylcholine content of yeast Golgi membranes, 10.1083/jcb.124.3.273
  52. Nourani A., Papajova D., Delahodde A., Jacq C., Clustered amino acid substitutions in the yeast transcription regulator Pdr3p increase pleiotropic drug resistance and identify a new central regulatory domain, 10.1007/s004380050583
  53. Monteoliva Lucía, Sánchez Miguel, Pla Jesús, Gil Concha, Nombela César, Cloning ofCandida albicans SEC14 gene homologue coding for a putative essential function, 10.1002/(sici)1097-0061(19960915)12:11<1097::aid-yea990>3.0.co;2-e
  54. Daum Günther, Paltauf Fritz, Phospholipid transfer in yeast. Isolation and partial characterization of a phospholipid transfer protein from yeast cytosol, 10.1016/0005-2760(84)90004-3
  55. Szolderits Günter, Hermetter Albin, Paltauf Fritz, Daum Günther, Membrane properties modulate the activity of a phosphatidylinositol transfer protein from the yeast, Saccharomyces cerevisiae, 10.1016/0005-2736(89)90481-1
Bibliographic reference van den Hazel, Bart H. ; Pichler, Harald ; do Valle Matta, Maria Adelaide ; Leitner, Erich ; Goffeau, André ; et. al. PDR16 and PDR17, two homologous genes of Saccharomyces cerevisiae, affect lipid biosynthesis and resistance to multiple drugs.. In: The Journal of biological chemistry, Vol. 274, no. 4, p. 1934-41 (1999)
Permanent URL http://hdl.handle.net/2078.1/12523