Roles of the C Terminus of Armadillo in Wingless Signaling in Drosophila

Corresponding author: Mark Peifer, Department of Biology, CB#3280, Coker Hall, University of North Carolina, Chapel Hill, NC 27599-3280., peifer{at}unc.edu (E-mail)

Communicating editor: V. G. FINNERTY

Drosophila melanogaster Armadillo and its vertebrate homolog ß-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 ß-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.

This article has been cited by other articles:

				C. Sustmann, H. Flach, H. Ebert, Q. Eastman, and R. Grosschedl Cell-Type-Specific Function of BCL9 Involves a Transcriptional Activation Domain That Synergizes with {beta}-Catenin Mol. Cell. Biol., May 15, 2008; 28(10): 3526 - 3537. [Abstract] [Full Text] [PDF]

				W. Xu and D. Kimelman Mechanistic insights from structural studies of beta-catenin and its binding partners J. Cell Sci., October 1, 2007; 120(19): 3337 - 3344. [Abstract] [Full Text] [PDF]

				G. Bellipanni, M. Varga, S. Maegawa, Y. Imai, C. Kelly, A. P. Myers, F. Chu, W. S. Talbot, and E. S. Weinberg Essential and opposing roles of zebrafish {beta}-catenins in the formation of dorsal axial structures and neurectoderm Development, April 1, 2006; 133(7): 1299 - 1309. [Abstract] [Full Text] [PDF]

				M. H. Price, D. M. Roberts, B. M. McCartney, E. Jezuit, and M. Peifer Cytoskeletal dynamics and cell signaling during planar polarity establishment in the Drosophila embryonic denticle J. Cell Sci., February 1, 2006; 119(3): 403 - 415. [Abstract] [Full Text] [PDF]

				C. J. Gottardi and B. M. Gumbiner Distinct molecular forms of {beta}-catenin are targeted to adhesive or transcriptional complexes J. Cell Biol., October 25, 2004; 167(2): 339 - 349. [Abstract] [Full Text] [PDF]

				R. Bauer, C. Lehmann, J. Martini, F. Eckardt, and M. Hoch Gap Junction Channel Protein Innexin 2 Is Essential for Epithelial Morphogenesis in the Drosophila Embryo Mol. Biol. Cell, June 1, 2004; 15(6): 2992 - 3004. [Abstract] [Full Text] [PDF]

				S. Hatsell, L. Medina, J. Merola, R. Haltiwanger, and P. Cowin Plakoglobin Is O-Glycosylated Close to the N-terminal Destruction Box J. Biol. Chem., September 26, 2003; 278(39): 37745 - 37752. [Abstract] [Full Text] [PDF]

				T. Y. Belenkaya, C. Han, H. J. Standley, X. Lin, D. W. Houston, J. Heasman, and X. Lin pygopus encodes a nuclear protein essential for Wingless/Wnt signaling Development, September 1, 2002; 129(17): 4089 - 4101. [Abstract] [Full Text] [PDF]

				D. A. Tice, W. Szeto, I. Soloviev, B. Rubinfeld, S. E. Fong, D. L. Dugger, J. Winer, P. M. Williams, D. Wieand, V. Smith, et al. Synergistic Induction of Tumor Antigens by Wnt-1 Signaling and Retinoic Acid Revealed by Gene Expression Profiling J. Biol. Chem., April 12, 2002; 277(16): 14329 - 14335. [Abstract] [Full Text] [PDF]

				M. Llimargas and P. A. Lawrence Seven Wnt homologues in Drosophila: A case study of the developing tracheae PNAS, November 15, 2001; (2001) 251304398. [Abstract] [Full Text] [PDF]

				N. S. Tolwinski and E. Wieschaus Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan Development, June 1, 2001; 128(11): 2107 - 2117. [Abstract] [Full Text] [PDF]

				I. Simcha, C. Kirkpatrick, E. Sadot, M. Shtutman, G. Polevoy, B. Geiger, M. Peifer, and A. Ben-Ze'ev Cadherin Sequences That Inhibit {beta}-Catenin Signaling: A Study in Yeast and Mammalian Cells Mol. Biol. Cell, April 1, 2001; 12(4): 1177 - 1188. [Abstract] [Full Text]

				J. Zhurinsky, M. Shtutman, and A. Ben-Ze'ev Differential Mechanisms of LEF/TCF Family-Dependent Transcriptional Activation by beta -Catenin and Plakoglobin Mol. Cell. Biol., June 15, 2000; 20(12): 4238 - 4252. [Abstract] [Full Text]

				K.-I. Takemaru and R. T. Moon The Transcriptional Coactivator CBP Interacts with {beta}-Catenin to Activate Gene Expression J. Cell Biol., April 17, 2000; 149(2): 249 - 254. [Abstract] [Full Text] [PDF]

				M Llimargas Wingless and its signalling pathway have common and separable functions during tracheal development Development, January 10, 2000; 127(20): 4407 - 4417. [Abstract] [PDF]

				J Zhurinsky, M Shtutman, and A Ben-Ze'ev Plakoglobin and beta-catenin: protein interactions, regulation and biological roles J. Cell Sci., January 9, 2000; 113(18): 3127 - 3139. [Abstract] [PDF]

				J. Wahl J. Cell Sci., January 5, 2000; 113(10): 1737 - 1745. [Abstract] [PDF]

				J Behrens Cross-regulation of the Wnt signalling pathway: a role of MAP kinases J. Cell Sci., January 3, 2000; 113(6): 911 - 919. [Abstract] [PDF]

				J. Piedra, D. Martinez, J. Castano, S. Miravet, M. Dunach, and A. G. de Herreros Regulation of beta -Catenin Structure and Activity by Tyrosine Phosphorylation J. Biol. Chem., June 1, 2001; 276(23): 20436 - 20443. [Abstract] [Full Text] [PDF]

				M. Llimargas and P. A. Lawrence Seven Wnt homologues in Drosophila: A case study of the developing tracheae PNAS, December 4, 2001; 98(25): 14487 - 14492. [Abstract] [Full Text] [PDF]