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Planta

, Volume 249, Issue 1, pp 49–57 | Cite as

From plant physiology to pharmacology: fusicoccin leaves the leaves

  • Lorenzo CamoniEmail author
  • Sabina Visconti
  • Patrizia Aducci
  • Mauro Marra
Review
  • 115 Downloads
Part of the following topical collections:
  1. Terpenes and Isoprenoids

Abstract

Main conclusion

This review highlights 50 years of research on the fungal diterpene fusicoccin, during which the molecule went from a tool in plant physiology research to a pharmacological agent in treating animal diseases.

Fusicoccin is a phytotoxic glycosylated diterpene produced by the fungus Phomopsis amygdali, a pathogen of almond and peach plants. Widespread interest in this molecule started when it was discovered that it is capable of causing stomate opening in all higher plants, thereby inducing wilting of leaves. Thereafter, FC became, and still is, a tool in plant physiology, due to its ability to influence a number of fundamental processes, which are dependent on the activation of the plasma membrane H+-ATPase. Molecular studies carried out in the last 20 years clarified details of the mechanism of proton pump stimulation, which involves the fusicoccin-mediated irreversible stabilization of the complex between the H+-ATPase and activatory 14-3-3 proteins. More recently, FC has been shown to influence cellular processes involving 14-3-3 binding to client proteins both in plants and animals. In this review, we report the milestones achieved in more than 50 years of research in plants and highlight recent advances in animals that have allowed this diterpene to be used as a 14-3-3 targeted drug.

Keywords

Diterpene phytotoxin Plasma membrane H+-ATPase, 14-3-3 proteins Protein–protein interaction Drug design 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

References

  1. Aducci P, Camoni L, Marra M, Visconti S (2002) From cytosol to organelles: 14-3-3 proteins as multifunctional regulators of plant cell. IUBMB Life 53:49–55Google Scholar
  2. Aitken A, Collinge DB, van Heusden BP, Isobe T, Roseboom PH, Rosenfeld G, Soll J (1992) 14-3-3 proteins: a highly conserved, widespread family of eukaryotic proteins. Trends Biochem Sci 17:498–501Google Scholar
  3. Anders C, Higuchi Y, Koschinsky K, Bartel M, Schumacher B, Thiel P, Nitta H, Preisig-Müller R, Schlichthörl G, Renigunta V, Ohkanda J, Daut J, Kato N, Ottmann C (2013) A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface. Chem Biol 20:583–593Google Scholar
  4. Ballio A, Chain EB, De Leo P, Erlanger BF, Mauri M, Tonolo A (1964) Fusicoccin: a new wilting toxin produced by Fusicoccum amygdali Del. Nature 203:296Google Scholar
  5. Ballio A, Brufani M, Casinovi CG, Cerrini S, Fedeli W, Pellicciari R, Santurbano B, Vaciago A (1968a) The structure of fusicoccin A. Experientia 24:631–635Google Scholar
  6. Ballio A, Carilli A, Santurbano B, Tuttobello L (1968b) Pilot plant production of fusicoccin. Ann Ist Super Sanita 4:317–332Google Scholar
  7. Barrow KD, Barton DHR, Chain EB, Ohnsorge UVF, Thomas R (1968) The constitution of fusicoccin. Chem Commun 1198–1200Google Scholar
  8. Barrow KD, Barton DHR, Chain EB, Ohnsorge UVF, Thomas R (1971) The constitution of fusicoccin. J Chem Soc C 1265–1273Google Scholar
  9. Baunsgaard L, Fuglsang AT, Jahn T, Korthout HA, de Boer AH, Palmgren MG (1998) The 14-3-3 proteins associate with the plant plasma membrane H(+)-ATPase to generate a fusicoccin binding complex and a fusicoccin responsive system. Plant J 13:661–671Google Scholar
  10. Blatt MR, Clint GM (1989) Mechanisms of fusicoccin action: kinetic modification and inactivation of K + channels in guard cells. Planta 178:509–523Google Scholar
  11. Bunney TD, De Boer AH, Levin M (2003) Fusicoccin signaling reveals 14-3-3 protein function as a novel step in left-right patterning during amphibian embryogenesis. Development 130:4847–4858Google Scholar
  12. Bury M, Andolfi A, Rogister B, Cimmino A, Mégalizzi V, Mathieu V, Feron O, Evidente A, Kiss R (2013a) Fusicoccin A, a phytotoxic carbotricyclic diterpene glucoside of fungal origin, reduces proliferation and invasion of glioblastoma cells by targeting multiple tyrosine kinases. Transl Oncol 6:112–123Google Scholar
  13. Bury M, Girault A, Mégalizzi V, Spiegl-Kreinecker S, Mathieu V, Berger W, Evidente A, Kornienko A, Gailly P, Vandier C, Kiss R (2013b) Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity. Cell Death Dis 4:e561Google Scholar
  14. Camoni L, Di Lucente C, Visconti S, Aducci P (2011) The phytotoxin fusicoccin promotes platelet aggregation via 14-3-3-glycoprotein Ib-IX-V interaction. Biochem J 436:429–436Google Scholar
  15. Camoni L, Visconti S, Aducci P (2013) The phytotoxin fusicoccin, a selective stabilizer of 14-3-3 interactions? IUBMB Life 65:513–517Google Scholar
  16. Camoni L, Visconti S, Aducci P, Marra M (2018) 14-3-3 proteins in plant hormone signaling: doing several things at once. Front Plant Sci 9:297Google Scholar
  17. Coblitz B, Wu M, Shikano S, Li M (2006) C-terminal binding: an expanded repertoire and function of 14-3-3 proteins. FEBS Lett 580:1531–1535Google Scholar
  18. de Boer AH (2002) Plant 14-3-3 proteins assist ion channels and pumps. Biochem Soc Trans 30:416–421Google Scholar
  19. de Boer AH, de Vries-van Leeuwen IJ (2012) Fusicoccanes: diterpenes with surprising biological functions. Trends Plant Sci 17:360–368Google Scholar
  20. De Michelis MI, Rasi-Caldogno F, Pugliarello MC, Olivari C (1991) Fusicoccin binding to its plasma membrane receptor and the activation of the plasma membrane H+-ATPase. Stimulation of the H+-ATPase in a plasma membrane fraction purified by phase partitioning. Bot Acta 104:265–271Google Scholar
  21. de Vries-van Leeuwen IJ, Kortekaas-Thijssen C, Nzigou Mandouckou JA, Kas S, Evidente A, de Boer AH (2010) Fusicoccin-A selectively induces apoptosis in tumor cells after interferon-alpha priming. Cancer Lett 293:198–206Google Scholar
  22. de Vries-van Leeuwen IJ, da Costa Pereira D, Flach KD, Piersma SR, Haase C, Bier D, Yalcin Z, Michalides R, Feenstra KA, Jiménez CR, de Greef TF, Brunsveld L, Ottmann C, Zwart W, de Boer AH (2013) Interaction of 14-3-3 proteins with the estrogen receptor alpha F domain provides a drug target interface. Proc Natl Acad Sci USA 110:8894–8899Google Scholar
  23. Dohrmann U, Hertel R, Pesci P, Cocucci SM, Marrè E, Randazzo G, Ballio A (1977) Localization of in vitro binding of the fungal toxin fusicoccin to plasma-membrane rich fractions from corn coleoptiles. Plant Sci Lett 9:291–299Google Scholar
  24. Freeman AK, Morrison DK (2011) 14-3-3 Proteins: diverse functions in cell proliferation and cancer progression. Semin Cell Dev Biol 22:681–687Google Scholar
  25. Fu H, Subramanian R, Masters SC (2000) 14-3-3s: structure function and regulation. Annu Rev Pharmacol Toxicol 40:617–647Google Scholar
  26. Fuglsang AT, Visconti S, Drumm K, Jahn T, Stensballe A, Mattei B, Jensen ON, Aducci P, Palmgren MG (1999) Binding of 14-3-3 protein to the plasma membrane H(+)-ATPase AHA2 involves the three C-terminal residues Tyr(946)-Thr-Val and requires phosphorylation of Thr(947). J Biol Chem 274:36774–36780Google Scholar
  27. Fullone MR, Visconti S, Marra M, Fogliano V, Aducci P (1998) Fusicoccin effect on the Interaction between plant 14-3-3 proteins and plasma membrane H -ATPase. J Biol Chem 273(13):7698–7702Google Scholar
  28. Giordanetto F, Schäfer A, Ottmann C (2014) Stabilization of protein-protein interactions by small molecules. Drug Discov Today 19:1812–1821Google Scholar
  29. Graniti A (1962) Phytotoxic action of Fusicoccum amygdali Del. On almond (Prunus amygdali St.). Phytopathol Mediterr 1:182–185Google Scholar
  30. Graniti A (1964) Some phytotoxicity data of fusicoccin A, a toxin produced in vitro by Fusicoccum amygdali Del. Phytopathol Mediterr 3:125–128Google Scholar
  31. Hermeking H (2003) The 14-3-3 cancer connection. Nat Rev Cancer 3:931–943Google Scholar
  32. Honma Y (2002) Cotylenin A—a plant growth regulator as a differentiation-inducing agent against myeloid leukemia. Leuk Lymphoma 43:1169–1178Google Scholar
  33. Honma Y, Akimoto M (2007) Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agents. Cancer Sci 98:1643–1651Google Scholar
  34. Huber SC, MacKintosh C, Kaiser WM (2002) Metabolic enzymes as targets for 14-3-3 proteins. Plant Mol Biol 50:1053–1063Google Scholar
  35. Jahn T, Fuglsang AT, Olsson A, Brüntrup IM, Collinge DB, Volkmann D, Sommarin M, Palmgren MG, Larsson C (1997) The 14-3-3 protein interacts directly with the C-terminal region of the plant plasma membrane H(+)-ATPase. Plant Cell 9:1805–1814Google Scholar
  36. Kaplan A, Morquette B, Kroner A, Leong S, Madwar C, Sanz R, Banerjee SL, Antel J, Bisson N, David S, Fournier AE (2017a) Small-molecule stabilization of 14-3-3 protein–protein interactions stimulates axon regeneration. Neuron 93:1082–1093.e5Google Scholar
  37. Kaplan A, Ottmann C, Fournier AE (2017b) 14-3-3 adaptor protein-protein interactions as therapeutic targets for CNS diseases. Pharmacol Res 125:114–121Google Scholar
  38. Kent CB, Shimada T, Ferraro GB, Ritter B, Yam PT, McPherson PS, Charron F, Kennedy TE, Fournier AE (2010) 14-3-3 proteins regulate protein kinase A activity to modulate growth cone turning responses. J Neurosci 30:14059–14067Google Scholar
  39. Korthout HA, de Boer AH (1994) A fusicoccin binding protein belongs to the family of 14-3-3 brain protein homologs. Plant Cell 6:1681–1692Google Scholar
  40. Lanfermeijer FC, Prins H (1994) Modulation of H + -atpase activity by fusicoccin in plasma membrane vesicles from Oat (Avena sativa L.) roots (a comparison of modulation by fusicoccin, trypsin, and lysophosphatidylcholine). Plant Physiol 104:1277–1285Google Scholar
  41. Liu D, Bienkowska J, Petosa C, Collier RJ, Fu H, Liddington R (1995) Crystal structure of the zeta isoform of the 14-3-3 protein. Nature 376:191–194Google Scholar
  42. Maki T, Kawamura A, Kato N, Ohkanda J (2013) Chemical ligation of epoxide-containing fusicoccins and peptide fragments guided by 14-3-3 protein. Mol BioSyst 9:940–943Google Scholar
  43. Marra M, Fullone MR, Fogliano V, Pen J, Mattei M, Masi S, Aducci P (1994) The 30-kilodalton protein present in purified fusicoccin receptor preparations is a 14-3-3-like protein. Plant Physiol 106:1497–1501Google Scholar
  44. Marra M, Fogliano V, Zambardi A, Fullone MR, Nasta D, Aducci P (1996) The H+-ATPase purified from maize root plasma membranes retains fusicoccin in vivo activation. FEBS Lett 382:293–296Google Scholar
  45. Marrè E (1979) Fusicoccin: a tool in plant physiology. Annu Rev Plant Physiol 30:273–288Google Scholar
  46. Meyer C, Waldkötter K, Sprenger A, Schlösser UG, Luther M, Weiler EW (1993) Survey of the taxonomic and tissue distribution of microsomal binding sites for the non-host selective fungal phytotoxin, fusicoccin. Z Naturforsch C 48:595–602Google Scholar
  47. Milroy LG, Brunsveld L, Ottmann C (2013) Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study. ACS Chem Biol 8:27–35Google Scholar
  48. Möbius N, Hertweck C (2009) Fungal phytotoxins as mediators of virulence. Curr Opin Plant Biol 12:390–398Google Scholar
  49. Molzan M, Kasper S, Röglin L, Skwarczynska M, Sassa T, Inoue T, Breitenbuecher F, Ohkanda J, Kato N, Schuler M, Ottmann C (2013) Stabilization of physical RAF/14-3-3 interaction by cotylenin A as treatment strategy for RAS mutant cancers. ACS Chem Biol 8:1869–1875Google Scholar
  50. Oecking C, Jaspert N (2009) Plant 14-3-3 proteins catch up with their mammalian orthologs. Curr Opin Plant Biol 12:760–765Google Scholar
  51. Oecking C, Eckerskorn C, Weiler EW (1994) The fusicoccin receptor of plants is a member of the 14-3-3 superfamily of eukaryotic regulatory proteins. FEBS Lett 352:163–166Google Scholar
  52. Oecking C, Piotrowski M, Hagemeier J, Hagemann K (1997) Topology and target interaction of the fusicoccin-binding 14-3-3 homologs of Commelina communis. Plant J 12:441–453Google Scholar
  53. Olivari C, Meanti C, De Michelis MI, Rasi-Caldogno F (1998) Fusicoccin binding to its plasma membrane receptor and the activation of the plasma membrane H(+)-ATPase. IV. Fusicoccin induces the association between the plasma membrane H(+)-ATPase and the fusicoccin receptor. Plant Physiol 116:529–537Google Scholar
  54. Ottmann C, Marco S, Jaspert N, Marcon C, Schauer N, Weyand M, Vandermeeren C, Duby G, Boutry M, Wittinghofer A, Rigaud JL, Oecking C (2007) Structure of a 14-3-3 coordinated hexamer of the plant plasma membrane H+-ATPase by combining X-ray crystallography and electron cryomicroscopy. Mol Cell 25:427–440Google Scholar
  55. Ottmann C, Weyand M, Sassa T, Inoue T, Kato N, Wittinghofer A, Oecking C (2009) A structural rationale for selective stabilization of anti-tumor interactions of 14-3-3 proteins by cotylenin A. J Mol Biol 386:913–919Google Scholar
  56. Ottmann C, Andrei SA, de Vink P, Sijbesma E, Han L, Brunsveld L, Kato N, Higuchi Y (2018) Rationally designed semi-synthetic natural product analogues for stabilization of 14-3-3 protein-protein interactions. Angew Chem Int Ed.  https://doi.org/10.1002/anie.201806584 Google Scholar
  57. Paiardini A, Aducci P, Cervoni L, Cutruzzolà F, Di Lucente C, Janson G, Pascarella S, Rinaldo S, Visconti S, Camoni L (2014) The phytotoxin fusicoccin differently regulates 14-3-3 proteins association to mode III targets. IUBMB Life 66:52–62Google Scholar
  58. Parvatkar P, Kato N, Uesugi M, Sato S, Ohkanda J (2015) Intracellular generation of a diterpene-peptide conjugate that inhibits 14-3-3-mediated interactions. J Am Chem Soc 137:15624–15627Google Scholar
  59. Pfeilmeier S, Caly DL, Malone JG (2016) Bacterial pathogenesis of plants: future challenges from a microbial perspective: challenges in bacterial molecular plant pathology. Mol Plant Pathol 17:1298–1313Google Scholar
  60. Piotrowski M, Morsomme P, Boutry M, Oecking C (1998) Complementation of the Saccharomyces cerevisiae plasma membrane H+-ATPase by a plant H+-ATPase generates a highly abundant fusicoccin binding site. J Biol Chem 273:30018–30023Google Scholar
  61. Rodolfo C, Rocco M, Cattaneo L, Tartaglia M, Sassi M, Aducci P, Scaloni A, Camoni L, Marra M (2016) ophiobolin A induces autophagy and activates the mitochondrial pathway of apoptosis in human melanoma cells. PLoS One 11:e0167672Google Scholar
  62. Saponaro A, Porro A, Chaves-Sanjuan A, Nardini M, Rauh O, Thiel G, Moroni A (2017) Fusicoccin activates KAT1 channels by stabilizing their interaction with 14-3-3 proteins. Plant Cell 29:2570–2580Google Scholar
  63. Sassa T, Togashi M, Kitaguchi T (1975) The structures of cotylenins A, B, C, D and E. Agric Biol Chem 39:1735–1744Google Scholar
  64. Stevers LM, Lam CV, Leysen SF, Meijer FA, van Scheppingen DS, de Vries RM, Carlile GW, Milroy LG, Thomas DY, Brunsveld L, Ottmann C (2016) Characterization and small-molecule stabilization of the multisite tandem binding between 14-3-3 and the R domain of CFTR. Proc Natl Acad Sci USA 113:E1152–E1161Google Scholar
  65. Sugawara F, Strobel G, Strange RN, Siedow JN, Van Duyne GD, Clardy J (1987) Phytotoxins from the pathogenic fungi Drechslera maydis and Drechslera sorghicola. Proc Natl Acad Sci USA 84:3081–3085Google Scholar
  66. Svennelid F, Olsson A, Piotrowski M, Rosenquist M, Ottman C, Larsson C, Oecking C, Sommarin M (1999) Phosphorylation of Thr-948 at the C terminus of the plasma membrane H(+)-ATPase creates a binding site for the regulatory 14-3-3 protein. Plant Cell 11:2379–2391Google Scholar
  67. Taoka K, Ohki I, Tsuji H, Furuita K, Hayashi K, Yanase T, Yamaguchi M, Nakashima C, Purwestri YA, Tamaki S, Ogaki Y, Shimada C, Nakagawa A, Kojima C, Shimamoto K (2011) 14-3-3 proteins act as intracellular receptors for rice Hd3a florigen. Nature 476:332–335Google Scholar
  68. Turner NC, Graniti A (1969) Fusicoccin: a fungal toxin that opens stomata. Nature 223:1070–1071Google Scholar
  69. Turner NC, Graniti A (1976) Stomatal response of two almond cultivars to fusicoccin. Physiol Plant Pathol 9:175–182Google Scholar
  70. Würtele M, Jelich-Ottmann C, Wittinghofer A, Oecking C (2003) Structural view of a fungal toxin acting on a 14-3-3 regulatory complex. EMBO J 22:987–994Google Scholar
  71. Xiao B, Smerdon SJ, Jones DH, Dodson GG, Soneji Y, Aitken A, Gamblin S (1995) Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. Nature 376:188–191Google Scholar
  72. Yaffe MB, Rittinger K, Volinia S, Caron PR, Aitken A, Leffers H, Gamblin SJ, Smerdon SJ, Cantley LC (1997) The structural basis for 14-3-3: phosphopeptide binding specificity. Cell 91:961–971Google Scholar
  73. Yam PT, Kent CB, Morin S, Farmer WT, Alchini R, Lepelletier L, Colman DR, Tessier-Lavigne M, Fournier AE, Charron F (2012) 14-3-3 proteins regulate a cell-intrinsic switch from sonic hedgehog-mediated commissural axon attraction to repulsion after midline crossing. Neuron 76:735–749Google Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiologyUniversity of Rome Tor VergataRomeItaly

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