Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1999 Sep;153(1):319–332. doi: 10.1093/genetics/153.1.319

Roles of the C terminus of Armadillo in Wingless signaling in Drosophila.

R T Cox 1, L M Pai 1, C Kirkpatrick 1, J Stein 1, M Peifer 1
PMCID: PMC1460731  PMID: 10471715

Abstract

Drosophila melanogaster Armadillo and its vertebrate homolog beta-catenin play multiple roles during development. Both are components of cell-cell adherens junctions and both transduce Wingless (Wg)/Wnt intercellular signals. The current model for Wingless signaling proposes that Armadillo binds the DNA-binding protein dTCF, forming a bipartite transcription factor that activates Wingless-responsive genes. In this model, Armadillo's C-terminal domain is proposed to serve an essential role as a transcriptional activation domain. In Xenopus, however, overexpression of C-terminally truncated beta-catenin activates Wnt signaling, suggesting that the C-terminal domain might not be essential. We reexamined the function of Armadillo's C terminus in Wingless signaling. We found that C-terminally truncated mutant Armadillo has a deficit in Wg-signaling activity, even when corrected for reduced protein levels. However, we also found that Armadillo proteins lacking all or part of the C terminus retain some signaling ability if overexpressed, and that mutants lacking different portions of the C-terminal domain differ in their level of signaling ability. Finally, we found that the C terminus plays a role in Armadillo protein stability in response to Wingless signal and that the C-terminal domain can physically interact with the Arm repeat region. These data suggest that the C-terminal domain plays a complex role in Wingless signaling and that Armadillo recruits the transcriptional machinery via multiple contact sites, which act in an additive fashion.

Full Text

The Full Text of this article is available as a PDF (897.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aberle H., Schwartz H., Hoschuetzky H., Kemler R. Single amino acid substitutions in proteins of the armadillo gene family abolish their binding to alpha-catenin. J Biol Chem. 1996 Jan 19;271(3):1520–1526. doi: 10.1074/jbc.271.3.1520. [DOI] [PubMed] [Google Scholar]
  2. Bauer A., Huber O., Kemler R. Pontin52, an interaction partner of beta-catenin, binds to the TATA box binding protein. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14787–14792. doi: 10.1073/pnas.95.25.14787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
  4. Brand A. H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. doi: 10.1242/dev.118.2.401. [DOI] [PubMed] [Google Scholar]
  5. Brannon M., Gomperts M., Sumoy L., Moon R. T., Kimelman D. A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes Dev. 1997 Sep 15;11(18):2359–2370. doi: 10.1101/gad.11.18.2359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brunner E., Peter O., Schweizer L., Basler K. pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. Nature. 1997 Feb 27;385(6619):829–833. doi: 10.1038/385829a0. [DOI] [PubMed] [Google Scholar]
  7. Cadigan K. M., Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997 Dec 15;11(24):3286–3305. doi: 10.1101/gad.11.24.3286. [DOI] [PubMed] [Google Scholar]
  8. Cavallo R. A., Cox R. T., Moline M. M., Roose J., Polevoy G. A., Clevers H., Peifer M., Bejsovec A. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature. 1998 Oct 8;395(6702):604–608. doi: 10.1038/26982. [DOI] [PubMed] [Google Scholar]
  9. Cox R. T., Kirkpatrick C., Peifer M. Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis. J Cell Biol. 1996 Jul;134(1):133–148. doi: 10.1083/jcb.134.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cox R. T., Pai L. M., Miller J. R., Orsulic S., Stein J., McCormick C. A., Audeh Y., Wang W., Moon R. T., Peifer M. Membrane-tethered Drosophila Armadillo cannot transduce Wingless signal on its own. Development. 1999 Mar;126(6):1327–1335. doi: 10.1242/dev.126.6.1327. [DOI] [PubMed] [Google Scholar]
  11. Fagotto F., Funayama N., Gluck U., Gumbiner B. M. Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus. J Cell Biol. 1996 Mar;132(6):1105–1114. doi: 10.1083/jcb.132.6.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Funayama N., Fagotto F., McCrea P., Gumbiner B. M. Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling. J Cell Biol. 1995 Mar;128(5):959–968. doi: 10.1083/jcb.128.5.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gallet A., Angelats C., Erkner A., Charroux B., Fasano L., Kerridge S. The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila. EMBO J. 1999 Apr 15;18(8):2208–2217. doi: 10.1093/emboj/18.8.2208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gallet A., Erkner A., Charroux B., Fasano L., Kerridge S. Trunk-specific modulation of wingless signalling in Drosophila by teashirt binding to armadillo. 1998 Jul 30-Aug 13Curr Biol. 8(16):893–902. doi: 10.1016/s0960-9822(07)00369-7. [DOI] [PubMed] [Google Scholar]
  15. Hsu S. C., Galceran J., Grosschedl R. Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin. Mol Cell Biol. 1998 Aug;18(8):4807–4818. doi: 10.1128/mcb.18.8.4807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huber A. H., Nelson W. J., Weis W. I. Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell. 1997 Sep 5;90(5):871–882. doi: 10.1016/s0092-8674(00)80352-9. [DOI] [PubMed] [Google Scholar]
  17. Karnovsky A., Klymkowsky M. W. Anterior axis duplication in Xenopus induced by the over-expression of the cadherin-binding protein plakoglobin. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4522–4526. doi: 10.1073/pnas.92.10.4522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klingensmith J., Noll E., Perrimon N. The segment polarity phenotype of Drosophila involves differential tendencies toward transformation and cell death. Dev Biol. 1989 Jul;134(1):130–145. doi: 10.1016/0012-1606(89)90084-5. [DOI] [PubMed] [Google Scholar]
  19. Larabell C. A., Torres M., Rowning B. A., Yost C., Miller J. R., Wu M., Kimelman D., Moon R. T. Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signaling pathway. J Cell Biol. 1997 Mar 10;136(5):1123–1136. doi: 10.1083/jcb.136.5.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Merriam J. M., Rubenstein A. B., Klymkowsky M. W. Cytoplasmically anchored plakoglobin induces a WNT-like phenotype in Xenopus. Dev Biol. 1997 May 1;185(1):67–81. doi: 10.1006/dbio.1997.8550. [DOI] [PubMed] [Google Scholar]
  21. Miller J. R., Moon R. T. Analysis of the signaling activities of localization mutants of beta-catenin during axis specification in Xenopus. J Cell Biol. 1997 Oct 6;139(1):229–243. doi: 10.1083/jcb.139.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Orsulic S., Peifer M. An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling. J Cell Biol. 1996 Sep;134(5):1283–1300. doi: 10.1083/jcb.134.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pai L. M., Kirkpatrick C., Blanton J., Oda H., Takeichi M., Peifer M. Drosophila alpha-catenin and E-cadherin bind to distinct regions of Drosophila Armadillo. J Biol Chem. 1996 Dec 13;271(50):32411–32420. doi: 10.1074/jbc.271.50.32411. [DOI] [PubMed] [Google Scholar]
  24. Peifer M., Orsulic S., Sweeton D., Wieschaus E. A role for the Drosophila segment polarity gene armadillo in cell adhesion and cytoskeletal integrity during oogenesis. Development. 1993 Aug;118(4):1191–1207. doi: 10.1242/dev.118.4.1191. [DOI] [PubMed] [Google Scholar]
  25. Peifer M., Pai L. M., Casey M. Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase. Dev Biol. 1994 Dec;166(2):543–556. doi: 10.1006/dbio.1994.1336. [DOI] [PubMed] [Google Scholar]
  26. Peifer M., Rauskolb C., Williams M., Riggleman B., Wieschaus E. The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation. Development. 1991 Apr;111(4):1029–1043. doi: 10.1242/dev.111.4.1029. [DOI] [PubMed] [Google Scholar]
  27. Peifer M., Sweeton D., Casey M., Wieschaus E. wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo. Development. 1994 Feb;120(2):369–380. doi: 10.1242/dev.120.2.369. [DOI] [PubMed] [Google Scholar]
  28. Peifer M., Wieschaus E. The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell. 1990 Dec 21;63(6):1167–1176. doi: 10.1016/0092-8674(90)90413-9. [DOI] [PubMed] [Google Scholar]
  29. Riese J., Yu X., Munnerlyn A., Eresh S., Hsu S. C., Grosschedl R., Bienz M. LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell. 1997 Mar 21;88(6):777–787. doi: 10.1016/s0092-8674(00)81924-8. [DOI] [PubMed] [Google Scholar]
  30. Rocheleau C. E., Downs W. D., Lin R., Wittmann C., Bei Y., Cha Y. H., Ali M., Priess J. R., Mello C. C. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell. 1997 Aug 22;90(4):707–716. doi: 10.1016/s0092-8674(00)80531-0. [DOI] [PubMed] [Google Scholar]
  31. Roose J., Molenaar M., Peterson J., Hurenkamp J., Brantjes H., Moerer P., van de Wetering M., Destrée O., Clevers H. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature. 1998 Oct 8;395(6702):608–612. doi: 10.1038/26989. [DOI] [PubMed] [Google Scholar]
  32. Rubenstein A., Merriam J., Klymkowsky M. W. Localizing the adhesive and signaling functions of plakoglobin. Dev Genet. 1997;20(2):91–102. doi: 10.1002/(SICI)1520-6408(1997)20:2<91::AID-DVG2>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
  33. Ruiz-Echevarria M. J., Czaplinski K., Peltz S. W. Making sense of nonsense in yeast. Trends Biochem Sci. 1996 Nov;21(11):433–438. doi: 10.1016/s0968-0004(96)10055-4. [DOI] [PubMed] [Google Scholar]
  34. Sanson B., White P., Vincent J. P. Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature. 1996 Oct 17;383(6601):627–630. doi: 10.1038/383627a0. [DOI] [PubMed] [Google Scholar]
  35. Suter B., Steward R. Requirement for phosphorylation and localization of the Bicaudal-D protein in Drosophila oocyte differentiation. Cell. 1991 Nov 29;67(5):917–926. doi: 10.1016/0092-8674(91)90365-6. [DOI] [PubMed] [Google Scholar]
  36. Thorpe C. J., Schlesinger A., Carter J. C., Bowerman B. Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. Cell. 1997 Aug 22;90(4):695–705. doi: 10.1016/s0092-8674(00)80530-9. [DOI] [PubMed] [Google Scholar]
  37. Vleminckx K., Kemler R., Hecht A. The C-terminal transactivation domain of beta-catenin is necessary and sufficient for signaling by the LEF-1/beta-catenin complex in Xenopus laevis. Mech Dev. 1999 Mar;81(1-2):65–74. doi: 10.1016/s0925-4773(98)00225-1. [DOI] [PubMed] [Google Scholar]
  38. van de Wetering M., Cavallo R., Dooijes D., van Beest M., van Es J., Loureiro J., Ypma A., Hursh D., Jones T., Bejsovec A. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell. 1997 Mar 21;88(6):789–799. doi: 10.1016/s0092-8674(00)81925-x. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES