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Adherens junctions and β-catenin-mediated cell signalling in a non-metazoan organism

Nature volume 408, pages 727–731 (2000)Cite this article

Abstract

Mechanical forces between cells have a principal role in the organization of animal tissues. Adherens junctions are an important component of these tissues, connecting cells through their actin cytoskeleton and allowing the assembly of tensile structures1,2,3,4. At least one adherens junction protein, β-catenin, also acts as a signalling molecule, directly regulating gene expression5,6,7. To date, adherens junctions have only been detected in metazoa, and therefore we looked for them outside the animal kingdom to examine their evolutionary origins. The non-metazoan Dictyostelium discoideum forms a multicellular, differentiated structure8. Here we describe the discovery of actin-associated intercellular junctions in Dictyostelium. We have isolated a gene encoding a β-catenin homologue, aardvark, which is a component of the junctional complex, and, independently, is required for cell signalling. Our discovery of adherens junctions outside the animal kingdom shows that the dual role of β-catenin in cell–cell adhesion and cell signalling evolved before the origins of metazoa.

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Figure 1: Identification of adherens junctions in the Dictyostelium fruiting body.
Figure 2: Direct visualization of the actin ring.
Figure 3: aardvark (aar ) encodes a homologue of β-catenin.
Figure 4: Analysis of a mutant that lacks the aar gene.
Figure 5: Aberrant cell differentiation in the aar mutant.

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References

  1. Stevenson, B. R. & Paul, D. L. The molecular constituents of intercellular junctions. Curr. Opin. Cell Biol. 1, 884–891 ( 1989).

    Article  CAS  Google Scholar 

  2. Ozawa, M., Ringwald, M. & Kemler, R. Uvomorulin–catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc. Natl Acad. Sci. USA 87, 4246– 4250 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Ozawa, M., Baribault, H. & Kemler, R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 8, 1711– 1717 (1989).

    Article  CAS  Google Scholar 

  4. Nagafuchi, A. & Takeichi, M. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 7, 3679–3684 (1988).

    Article  CAS  Google Scholar 

  5. Behrens, J. et al. Functional interaction of β-catenin with the transcription factor LEF–1. Nature 382, 638– 642 (1996).

    Article  ADS  CAS  Google Scholar 

  6. Molenaar, M. et al. XTcf-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell 86, 391–399 (1996).

    Article  CAS  Google Scholar 

  7. Huber, O. et al. Nuclear localization of β-catenin by interaction with transcription factor LEF-1. Mech. Dev. 59, 3– 10 (1996).

    Article  CAS  Google Scholar 

  8. Raper, K. B. Dictyostelium discoideum, a new species of slime mold from decaying forest leaves. J. Agr. Res. 50, 135– 147 (1935).

    Google Scholar 

  9. Pang, K. M., Lee, E. & Knecht, D. A. Use of a fusion protein between GFP and an actin-binding domain to visualize transient filamentous-actin structures. Curr. Biol. 8, 405–408 ( 1998).

    Article  CAS  Google Scholar 

  10. Nathke, I. S., Hinck, L., Swedlow, J. R., Papkoff, J. & Nelson, W. J. Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells. J. Cell Biol. 125, 1341–1352 (1994).

    Article  CAS  Google Scholar 

  11. Morio, T. et al. The Dictyostelium developmental cDNA project: generation and analysis of expressed sequence tags from the first-finger stage of development. DNA Res. 5, 335–340 (1998).

    Article  CAS  Google Scholar 

  12. Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).

    Article  CAS  Google Scholar 

  13. Aberle, H., Schwartz, H., Hoschuetzky, H. & Kemler, R. Single amino acid substitutions in proteins of the armadillo gene family abolish their binding to α-catenin. J. Biol. Chem. 271 , 1520–1526 (1996).

    Article  CAS  Google Scholar 

  14. Wang, Y. X., Catlett, N. L. & Weisman, L. S. Vac8p, a vacuolar protein with armadillo repeats, functions in both vacuole inheritance and protein targeting from the cytoplasm to vacuole. J. Cell Biol. 140, 1063– 1074 (1998).

    Article  CAS  Google Scholar 

  15. Fleckenstein, D., Rohde, M., Klionsky, D. J. & Rüdiger, M. Yel013p (Vac8p), an armadillo repeat protein related to plakoglobin and importin-α, is associated with the yeast vacuole membrane. J. Cell Sci. 111, 3109–3118 (1998).

    CAS  PubMed  Google Scholar 

  16. Pan, X. & Goldfarb, D. S. YEB3/VAC8 encodes a myristylated armadillo protein of the Saccharomyces cerevisiae vacuolar membrane that functions in vacuole fusion and inheritance. J. Cell Sci. 111, 2137–2147 ( 1998).

    CAS  PubMed  Google Scholar 

  17. Williams, J. G. et al. Origins of the prestalk-prespore pattern in Dictyostelium development. Cell 59, 1157– 1163 (1989).

    Article  MathSciNet  CAS  Google Scholar 

  18. Harwood, A. J., Plyte, S. E., Woodgett, J., Strutt, H. & Kay, R. R. Glycogen synthase kinase 3 regulates cell fate in Dictyostelium. Cell 80, 139–148 (1995).

    Article  CAS  Google Scholar 

  19. Plyte, S. E., O'Donovan, E., Woodgett, J. R. & Harwood, A. J. Glycogen synthase kinase-3 (GSK-3) is regulated during Dictyostelium development via the serpentine receptor cAR3. Development 126, 325–333 (1999).

    CAS  PubMed  Google Scholar 

  20. Sokol, S. Y. Wnt signaling and dorso-ventral axis specification in vertebrates. Curr. Opin. Genet. Dev. 9, 405–410 (1999).

    Article  CAS  Google Scholar 

  21. Rocheleau, C. E. et al. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90, 707–716 (1997).

    Article  CAS  Google Scholar 

  22. Schlesinger, A., Shelton, C. A., Maloof, J. N., Meneghini, M. & Bowerman, B. Wnt pathway components orient a mitotic spindle in the early Caenorhabditis elegans embryo without requiring gene transcription in the responding cell. Genes Dev. 13, 2028–2038 ( 1999).

    Article  CAS  Google Scholar 

  23. Korswagen, H. C., Herman, M. A. & Clevers, H. C. Distinct β-catenins mediate adhesion and signalling functions in C. elegans. Nature 406, 527–532 (2000).

    Article  ADS  CAS  Google Scholar 

  24. Manstein, D. J., Schuster, H. P., Morandini, P. & Hunt, D. M. Cloning vectors for the production of proteins in Dictyostelium discoideum . Gene 162, 129–134 (1995).

    Article  CAS  Google Scholar 

  25. Howard, P. K., Ahern, K. G. & Firtel, R. A. Establishment of a transient expression system for Dictyostelium discoideum. Nucleic Acids Res. 16 , 2613–2623 (1988).

    Article  CAS  Google Scholar 

  26. Strafstrom, J. & Steahelin, L. Antibody localisation of extensin in cell walls of carrot storage roots. Planta 174, 321–332 ( 1988).

    Article  Google Scholar 

  27. Kim, L., Liu, J. & Kimmel, A. R. The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate specification. Cell 99, 399– 408 (1999).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. Staehelin, who suggested that we examine the stalk pinch region for an actin ring. We would also like to thank R. Williams and E. Dalton for their help with making DNA constructs; and D. Knight, V. Braga, R. Kay and J. Hyams for their advice and comments. J.C.C. was supported by a MRC/GlaxoWellcome Studentship. J.P.R. is a Wellcome Prize Student and A.J.H. is a Wellcome Trust Senior Fellow. This work was partly funded by a NATO collaborative research grant, the research enhancement fund of the College of Arts and Sciences, Texas Tech University, and departmental and university funds to the Department of Biological Sciences Electron Microscopy Laboratory at Texas Tech University.

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  1. Juliet C. Coates

    Present address: MRC, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

  2. Mark J. Grimson, Juliet C. Coates, Jonathan P. Reynolds, Mark Shipman and Adrian J. Harwood: These authors contributed equally to this work.

Authors and Affiliations

  1. Dept of Biological Sciences, Texas Tech University, Lubbock, 79409, Texas, USA

    Mark J. Grimson & Richard L. Blanton

  2. MRC Laboratory for Molecular Cell Biology, University College London, Gower St, London, WC1E 6BT, UK

    Juliet C. Coates, Jonathan P. Reynolds, Mark Shipman & Adrian J. Harwood

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Correspondence to Adrian J. Harwood.

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Grimson, M., Coates, J., Reynolds, J. et al. Adherens junctions and β-catenin-mediated cell signalling in a non-metazoan organism. Nature 408, 727–731 (2000). https://doi.org/10.1038/35047099

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