Planta

, 234:903 | Cite as

Peroxisomal localisation of the final steps of the mevalonic acid pathway in planta

  • Andrew J. Simkin
  • Grégory Guirimand
  • Nicolas Papon
  • Vincent Courdavault
  • Insaf Thabet
  • Olivia Ginis
  • Sadok Bouzid
  • Nathalie Giglioli-Guivarc’h
  • Marc Clastre
Original Article

Abstract

In plants, the mevalonic acid (MVA) pathway provides precursors for the formation of triterpenes, sesquiterpenes, phytosterols and primary metabolites important for cell integrity. Here, we have cloned the cDNA encoding enzymes catalysing the final three steps of the MVA pathway from Madagascar periwinkle (Catharanthus roseus), mevalonate kinase (MVK), 5-phosphomevalonate kinase (PMK) and mevalonate 5-diphosphate decarboxylase (MVD). These cDNA were shown to functionally complement MVA pathway deletion mutants in the yeast Saccharomyces cerevisiae. Transient transformations of C. roseus cells with yellow fluorescent protein (YFP)-fused constructs reveal that PMK and MVD are localised to the peroxisomes, while MVK was cytosolic. These compartmentalisation results were confirmed using the Arabidopsis thaliana MVK, PMK and MVD sequences fused to YFP. Based on these observations and the arguments raised here we conclude that the final steps of the plant MVA pathway are localised to the peroxisome.

Keywords

Arabidopsis Catharanthus Isoprenoid Mevalonic acid pathway Peroxisome 

Abbreviations

AACT

Acetoacetyl-CoA thiolase

FOA

5-fluoroorotic acid

HMGR

3-hydroxy-3-methylglutaryl-CoA reductase

HMGS

3-hydroxy-3-methylglutaryl-CoA synthase

IDI

Isopentenyl diphosphate isomerase

MVA

Mevalonic acid

MVD

Mevalonate 5-diphosphate decarboxylase

MVK

Mevalonate kinase

PMK

5-phosphomevalonate kinase

PTS

Peroxisomal targeting signal

YFP

Yellow fluorescent protein

Supplementary material

425_2011_1444_MOESM1_ESM.doc (234 kb)
Supplementary material 1 (DOC 234 kb)
425_2011_1444_MOESM2_ESM.doc (76 kb)
Supplementary material 2 (DOC 76 kb)
425_2011_1444_MOESM3_ESM.doc (72 kb)
Supplementary material 3 (DOC 71 kb)

References

  1. Ahumada I, Cairo A, Hemmerlin A, Gonzalez V, Pateraki I, Bach TJ, Rodriguez-Concepcion M, Campos N, Boronat A (2008) Characterization of the gene family encoding acetoacetyl-CoA thiolase in Arabidopsis. Funct Plant Biol 35:1100–1111CrossRefGoogle Scholar
  2. Bouvier F, Rahier A, Camara B (2005) Biogenesis, molecular regulation and function of plant isoprenoids. Prog Lipid Res 44:357–429PubMedCrossRefGoogle Scholar
  3. Campos N, Boronat A (1995) Targeting and topology in the membrane of plant 3-hydroxy-3-methylglutaryl coenzyme A reductase. Plant Cell 7:2163–2174PubMedCrossRefGoogle Scholar
  4. Carrie C, Murcha MW, Millar AH, Smith SM, Whelan J (2007) Nine 3-ketoacyl-CoA thiolases (KATs) and acetoacetyl-CoA thiolases (ACATs) encoded by five genes in Arabidopsis thaliana are targeted either to peroxisomes or cytosol but not to mitochondria. Plant Mol Biol 63:97–108PubMedCrossRefGoogle Scholar
  5. Cordier H, Karst F, Bergès T (1999) Heterologous expression in Saccharomyces cerevisiae of an Arabidopsis thaliana cDNA encoding mevalonate diphosphate decarboxylase. Plant Mol Biol 39:953–967PubMedCrossRefGoogle Scholar
  6. Dewick PM (2002) The biosynthesis of C5–C25 terpenoid compounds. Nat Prod Rep 19:181–222PubMedCrossRefGoogle Scholar
  7. Gershenzon J, Dudareva N (2007) The function of terpene natural products in the natural world. Nat Chem Biol 3:408–414PubMedCrossRefGoogle Scholar
  8. Guirimand G, Burlat V, Oudin A, Lanoue A, St-Pierre B, Courdavault V (2009) Optimization of the transient transformation of Catharanthus roseus cells by particle bombardment and its application to the subcellular localization of hydroxymethylbutenyl 4-diphosphate synthase and geraniol 10-hydroxylase. Plant Cell Rep 28:1215–1234PubMedCrossRefGoogle Scholar
  9. Guirimand G, Courdavault V, Lanoue A, Mahroug S, Guihur A, Blanc N, Giglioli-Guivarc’h N, St-Pierre B, Burlat V (2010) Strictosidine activation in Apocynaceae: towards a “nuclear time bomb”? BMC Plant Biol 10:182PubMedGoogle Scholar
  10. Hayashi H, De Bellis L, Hayashi Y, Nito K, Kato A, Hayashi M, Hara-Nishimura I, Nishimura M (2002) Molecular characterization of an Arabidopsis acyl-coenzyme a synthetase localized on glyoxysomal membranes. Plant Physiol 130:2019–2026PubMedCrossRefGoogle Scholar
  11. Hedhili S, Courdavault V, Giglioli-Guivarc’h N, Gantet P (2007) Regulation of the terpene moiety biosynthesis of Catharanthus roseus terpene indole alkaloids. Phytochem Rev 6:341–351CrossRefGoogle Scholar
  12. Hemmerlin A, Hoeffler JF, Meyer O, Tritsch D, Kagan IA, Grosdemange-Billiard C, Rohmer M, Bach TJ (2003) Cross-talk between the cytosolic mevalonate and the plastidial methylerythritol phosphate pathways in tobacco bright yellow-2 cells. J Biol Chem 278:26666–26676PubMedCrossRefGoogle Scholar
  13. Hogenboom S, Tuyp JJM, Espeel M, Koster J, Wanders RJA, Waterham HR (2004a) Mevalonate kinase is a cytosolic enzyme in humans. J Cell Sci 117:631–639PubMedCrossRefGoogle Scholar
  14. Hogenboom S, Tuyp JJM, Espeel M, Koster J, Wanders RJA, Waterham HR (2004b) Phosphomevalonate kinase is a cytosolic protein in humans. J Lipid Res 45:697–705PubMedCrossRefGoogle Scholar
  15. Hogenboom S, Tuyp JJM, Espeel M, Koster J, Wanders RJA, Waterham HR (2004c) Human mevalonate pyrophosphate decarboxylase is localized in the cytosol. Mol Genet Metab 81:216–224PubMedCrossRefGoogle Scholar
  16. Hsieh M, Chang C, Hsu S, Chen J (2008) Chloroplast localization of methylerythritol 4-phosphate pathway enzymes and regulation of mitochondrial genes in ispD and ispE albino mutants in Arabidopsis. Plant Mol Biol 66:663–673PubMedCrossRefGoogle Scholar
  17. Kaur N, Reumann S, Hu J (2009) Peroxisome biogenesis and function: September 11, 2009. The Arabidopsis book. American Society of Plant Biologists, Rockville. doi:10.1199/tab.0123. http://www.aspb.org/publications/arabidopsis/
  18. Kovacs WJ, Tape KN, Shackelford JE, Duan X, Kasumov T, Kelleher JK, Brunengraber H, Krisans SK (2007) Localization of the pre-squalene segment of the isoprenoid biosynthetic pathway in mammalian peroxisomes. Histochem Cell Biol 127:273–290PubMedCrossRefGoogle Scholar
  19. Lamberto I, Percudani R, Gatti R, Folli C, Petrucco S (2010) Conserved alternative splicing of Arabidopsis transthyretin-like determines protein localization and S-allantoin synthesis in peroxisomes. Plant Cell 22:1564–1574PubMedCrossRefGoogle Scholar
  20. Leivar P, Gonzalez VM, Castel S, Trelease RN, Lopez-Iglesias C, Arro M, Boronat A, Campos N, Ferrer A, Fernandez-Busquets X (2005) Subcellular localization of Arabidopsis 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Plant Physiol 137:57–69PubMedCrossRefGoogle Scholar
  21. Luo B, Norris C, Bolstad ES, Knecht DA, Grant DF (2008) Protein quaternary structure and expression levels contribute to peroxisomal-targeting-sequence-1-mediated peroxisomal import of human soluble epoxide hydrolase. J Mol Biol 380:31–41PubMedCrossRefGoogle Scholar
  22. Merret R, Cirioni JR, Bach TJ, Hemmerlin A (2007) A serine involved in actin-dependent subcellular localization of a stress-induced tobacco BY-2 hydroxymethylglutaryl-CoA reductase isoform. FEBS Lett 581:5295–5299PubMedCrossRefGoogle Scholar
  23. Mizuno Y, Kurochkin IV, Herberth M, Okazaki Y, Schönbach C (2008) Predicted mouse peroxisome-targeted proteins and their actual subcellular locations. BMC Bioinformatics 9(Suppl 12):S16PubMedCrossRefGoogle Scholar
  24. Nagegowda DA, Ramalingam S, Hemmerlin A, Bach TJ, Chye ML (2005) Brassica juncea HMG-CoA synthase: localization of mRNA and protein. Planta 221:844–856PubMedCrossRefGoogle Scholar
  25. Nelson BK, Cai X, Nebenführ A (2007) A multicolored set of in vivo organelle markers for co-localization studies in Arabidopsis and other plants. Plant J 51:1126–1136PubMedCrossRefGoogle Scholar
  26. Olivier LM, Chambliss KL, Gibson KM, Krisans SK (1999) Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting. J Lipid Res 40:672–679PubMedGoogle Scholar
  27. Olivier LM, Kovacs W, Masuda K, Keller GA, Krisans SK (2000) Identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes. AA-CoA thiolase, HMG-CoA synthase, MPPD, and FPP synthase. J Lipid Res 41:1921–1935PubMedGoogle Scholar
  28. Oudin A, Courtois M, Rideau M, Clastre M (2007) The iridoid pathway in Catharanthus roseus alkaloid biosynthesis. Phytochem Rev 6:259–276CrossRefGoogle Scholar
  29. Pan X, Yuan DS, Xiang D, Wang X, Sookhai-Mahadeo S, Bader JS, Hieter P, Spencer F, Boeke JD (2004) A robust toolkit for functional profiling of the yeast genome. Mol Cell 16:487–496PubMedCrossRefGoogle Scholar
  30. Petriv OI, Tang L, Titorenko VI, Rachubinski RA (2004) A new definition for the consensus sequence of the peroxisome targeting signal type 2. J Mol Biol 341:119–134PubMedCrossRefGoogle Scholar
  31. Reumann S (2004) Specification of the peroxisome targeting signals type 1 and type 2 of plant peroxisomes by bioinformatics analyses. Plant Physiol 135:783–800PubMedCrossRefGoogle Scholar
  32. Reumann S, Babujee L, Ma C, Wienkoop S, Siemsen T, Antonicelli GE, Rasche N, Lüder F, Weckwerth W, Jahn O (2007) Proteome analysis of Arabidopsis leaf peroxisomes reveals novel targeting peptides, metabolic pathways, and defense mechanisms. Plant Cell 19:3170–3793PubMedCrossRefGoogle Scholar
  33. Reumann S, Quan S, Aung K, Yang P, Manandhar-Shrestha K, Holbrook D, Linka N, Switzenberg R, Wilkerson CG, Weber AP, Olsen LJ, Hu J (2009) In-depth proteome analysis of Arabidopsis leaf peroxisomes combined with in vivo subcellular targeting verification indicates novel metabolic and regulatory functions of peroxisomes. Plant Physiol 150:125–143PubMedCrossRefGoogle Scholar
  34. Riou C, Tourte Y, Lacroute F, Karst F (1994) Isolation and characterization of a cDNA encoding Arabidopsis thaliana mevalonate kinase by genetic complementation in yeast. Gene 148:293–297PubMedCrossRefGoogle Scholar
  35. Rodriguez-Concepcion M (2006) Early steps in isoprenoid biosynthesis: multilevel regulation of the supply of common precursors in plant cells. Phytochem Rev 5:1–15CrossRefGoogle Scholar
  36. Rodriguez-Concepcion M, Boronat A (2002) Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics. Plant Physiol 130:1079–1089PubMedCrossRefGoogle Scholar
  37. Sando T, Takaoka C, Mukal Y, Yamashita A, Hattori M, Ogasawara N, Fukusaki E, Kobayashi A (2008) Cloning and characterisation of mevalonate pathway genes in a natural rubber producing plant, Hevea brasiliensis. Biosci Biotechnol Biochem 72:2049–2060PubMedCrossRefGoogle Scholar
  38. Sapir-Mir M, Mett A, Belausov E, Tal-Meshulam S, Frydman A, Gidoni D, Eyal Y (2008) Peroxisomal localization of Arabidopsis isopentenyl diphosphate isomerases suggests that part of the plant isoprenoid mevalonic acid pathway is compartmentalized to peroxisomes. Plant Physiol 148:1219–1228PubMedCrossRefGoogle Scholar
  39. Schrader M, Fahimi HD (2008) The peroxisome: still a mysterious organelle. Histochem Cell Biol 129:421–440PubMedCrossRefGoogle Scholar
  40. Tian GW, Mohanty A, Chary SN, Li S, Paap B, Drakakaki G, Kopec CD, Li J, Ehrhardt D, Jackson D, Rhee SY, Raikhel NV, Citovsky V (2004) High-throughput fluorescent tagging of full-length Arabidopsis gene products in planta. Plant Physiol 135:25–38PubMedCrossRefGoogle Scholar
  41. van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R (2004) The Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem 11:607–628CrossRefGoogle Scholar
  42. Wolf J, Schliebs W, Erdmann R (2010) Peroxisomes as dynamic organelles: peroxisomal matrix protein import. FEBS J 277:3268–3278PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Andrew J. Simkin
    • 1
  • Grégory Guirimand
    • 1
  • Nicolas Papon
    • 1
  • Vincent Courdavault
    • 1
  • Insaf Thabet
    • 1
    • 2
  • Olivia Ginis
    • 1
  • Sadok Bouzid
    • 2
  • Nathalie Giglioli-Guivarc’h
    • 1
  • Marc Clastre
    • 1
  1. 1.EA 2106, Biomolécules et Biotechnologies VégétalesUniversité François-Rabelais de ToursToursFrance
  2. 2.Laboratoire de Biotechnologie et Physiologie Végétale, Département des Sciences BiologiquesFaculté des Sciences de TunisTunisTunisia

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