Dictyostelium as a Biomedical Model

Abstract

The social amoeba, Dictyostelium discoideum, has been commonly used to investigate cell motility, signal transduction, cell type differentiation and development. With the recent completion of the genome and the increasing number of experimental tools available for the organism, it has now become an attractive model for examining some well‚Äźdefined biomedical questions.

Keywords: amoeba; cancer; medical research; model systems; neuroprotection; pharmacogenetics

Figure 1.

Dictyostelium discoideum, a simple eukaryotic amoeba. (a) Dictyostelium is found in leaf litter on forest floors. The mature fruiting body is around 1 mm tall, and composed of spore head, stalk and basal disc cells. Bar, 0.5 mm. Kindly provided by Owen Gilbert. (b) It can be cultured in the laboratory on a bacterial lawn whereby single cells form circular isogenic plaques as shown, or in liquid culture. (c) Dictyostelium single cells, here showing one cell expressing a green fluorescent‐tagged cytosolic protein (prolyl oligopeptidase). Bar, 10 μm. Reproduced from Williams , by permission of Elsevier.

Figure 2.

Dictyostelium can be used for analysis of drug‐sensitive signalling pathways and drug targets. (a) Wild‐type cells form fruiting bodies over a 24‐h period. (b) The drug valproic acid, a short chain fatty acid used for bipolar disorder and epilepsy treatment, blocks cell aggregation at 1 mM – close to therapeutic concentrations. (c) Use of a clonal line of Dictyostelium containing a dominant active protein kinase A (PKA) enzyme overcomes this block, suggesting the signalling pathway containing this enzyme may be reduced by the drug. (d) Dictyostelium cells form immature fruiting bodies after 18 h of development, a process which is also blocked (e) in the presence of 0.5 mM VPA or (f) with novel drugs based around the structure of VPA. Bar, 0.5 mm. See also Boeckeler et al., .

close

References

Adley K, Keim M and Williams RSB (2005) Pharmacogenetics: defining the genetic basis of drug action and inositol trisphosphate analysis. In: Eichinger L and Rivero F (eds) Methods in Molecular Biology: Dictyostelium discoideum, pp. 517–534. Totowa, NJ: The Humana Press Inc.

Boeckeler K, Adley K, Xu X et al. (2006) The neuroprotective agent, valproic acid, regulates the mitogen‐activated protein kinase pathway through modulation of protein kinase A signalling in Dictyostelium discoideum. European Journal of Cell Biology 85: 1047–1057.

Bokko PB, Francione L, Bandala‐Sanchez E et al. (2007) Diverse cytopathologies in mitochondrial disease are caused by AMPK signalling. Molecular Biology of the Cell 18(5): 1874–1886.

Dormann D, Weijer G, Parent CA, Devreotes PN and Weijer CJ (2002) Visualizing PI3 kinase‐mediated cell–cell signaling during Dictyostelium development. Current Biology 12: 1178–1188.

Eichinger L, Pachebat JA and Glockner G (2005) The genome of the social amoeba Dictyostelium discoideum. Nature 435: 43–57.

Faix J, Kreppel L, Shaulsky G, Schleicher M and Kimmel AR (2004) A rapid and efficient method to generate multiple gene disruptions in Dictyostelium discoideum using a single selectable marker and the Cre‐LoxP system. Nucleic Acids Research 32: e143.

Farbrother P, Wagner C, Na J et al. (2007) Dictyostelium transcriptional host cell response upon infection with Legionella. Cell Microbiology 3: 438–456.

Fischer M, Haase I, Wiesner S and Muller‐Taubenberger A (2006) Visualizing cytoskeleton dynamics in mammalian cells using a humanized variant of monomeric red fluorescent protein. FEBS Letters 580: 2495–2502.

Fortini ME, Skupski MP, Boguski MS and Hariharan IK (2000) A survey of human disease gene counterparts in the Drosophila genome. Journal of Cell Biology 150: F23–F30.

Glöckner G, Eichinger L, Szafranski K et al. (2002) Sequence and analysis of chromosome 2 of Dictyostelium discoideum. Nature 418: 79–85.

Gräf R, Daunderer C and Schliwa M (2000) Dictyostelium DdCP224 is a microtubule‐associated protein and a permanent centrosomal resident involved in centrosome duplication. Journal of Cell Science 113: 1747–1758.

Hudock MP, Sanz‐Rodriguez CE, Song Y et al. (2007) Inhibition of Trypanosoma cruzi hexokinase by bisphosphonates. Journal of Medicinal Chemistry 12: 215–223.

Kuspa A and Loomis WF (1992) Tagging developmental genes in Dictyostelium by restriction enzyme‐mediated integration of plasmid DNA. Proceedings of the National Academy of Sciences of the USA 89: 8803–8807.

Laguna RK, Creasey EA, Li Z, Valtz N and Isberg RR (2006) A Legionella pneumophila‐translocated substrate that is required for growth within macrophages and protection from host cell death. Proceedings of the National Academy of Sciences of the USA 103: 18745–18750.

Mahadeo DC, Janka‐Junttila M, Smoot RL, Roselova P and Parent CA (2007) A chemoattractant‐mediated Gi‐coupled pathway activates adenylyl cyclase in human neutrophils. Molecular Biology of the Cell 18: 512–522.

Min J, Van Veldhoven PP, Zhang L et al. (2005) Sphingosine‐1‐phosphate lyase regulates sensitivity of human cells to select chemotherapy drugs in a P38‐dependent manner. Molecular Cancer Research 3: 287–296.

Nellen W, Silan C and Firtel RA (1984) DNA‐mediated transformation in Dictyostelium discoideum: regulated expression of an actin gene fusion. Molecular Cell Biology 4: 2890–2898.

Parent CA, Blacklock BJ, Froehlich WM, Murphy DB and Devreotes PN (1998) G protein signaling events are activated at the leading edge of chemotactic cells. Cell 95: 81–91.

Popova B, Kuhlmann M, Hinas A, Soderbom F and Nellen W (2006) HelF, a putative RNA helicase acts as a nuclear suppressor of RNAi but not antisense mediated gene silencing. Nucleic Acids Research 34: 773–784.

Raper KB (1935) Dictyostelium discoideum, a new species of slime mold from decaying forest leaves. Journal of Agricultural Research 50: 135–147.

Schilde C, Araki T, Williams H, Harwood A and Williams JG (2004) GSK3 is a multifunctional regulator of Dictyostelium development. Development 131: 4555–4565.

Unal C and Steinert M (2006) Dictyostelium discoideum as a model to study host–pathogen interactions. Methods in Molecular Biology 346: 507–515.

Weijer CJ and Williams JG (2001) Dictyostelium: cell sorting and patterning. In: eLS. Chichester: Wiley. doi: 10.1038/npg.els.0002579.

Wessels D, Srikantha T, Yi S et al. (2006) The Shwachman‐Bodian‐Diamond syndrome gene encodes an RNA‐binding protein that localizes to the pseudopod of Dictyostelium amoebae during chemotaxis. Journal of Cell Science 119: 370–379.

Williams RS, Boeckeler K, Graf R et al. (2006) Towards a molecular understanding of human diseases using Dictyostelium discoideum. Trends in Molecular Medicine 12: 415–424.

Williams RSB (2005) Pharmacogenetics in model systems: defining a common mechanism of action for mood stabilisers. Progress in Neuro‐psychopharmacology and Biological Psychiatry 29: 1029–1037.

Williams RSB, Cheng L, Mudge AW and Harwood AJ (2002) A common mechanism of action for three mood‐stabilizing drugs. Nature 417: 292–295.

Further Reading

Eichinger L and Rivero F (eds) (2006) Dictyostelium discoideum protocols. In: Methods in Molecular Biology, vol. 346. Totowa, NJ: Humana Press Inc.

Kessin RH (2001) Dictyostelium – Evolution, Cell Biology, and the Development of Multicellularity. Cambridge, UK: Cambridge University Press.

Maniak M and Nellen W (2004) Dictyostelium: cell culture and molecular tools. In: eLS. Chichester: Wiley. http://www.els.net/ [doi: 10.1038/npg.els.0002579]

Williams RSB (2005) Pharmacogenetics in model systems: defining a common mechanism of action for mood stabilizers. Progress in Neuro‐psychopharmacology and Biological Psychiatry 29: 1029–1037.

Williams RSB, Boeckeler K, Gräf R et al. (2006) Towards a molecular understanding of human diseases using Dictyostelium discoideum. Trends in Molecular Medicine 12: 415–424.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Boeckeler, Katrina, and Williams, Robin SB(Sep 2007) Dictyostelium as a Biomedical Model. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006038]