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

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.

Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor.

The adenomatous polyposis coli (APC) tumour-suppressor protein controls the Wnt signalling pathway by forming a complex with glycogen synthase kinase 3beta (GSK-3beta), axin/conductin and betacatenin. Complex formation induces the rapid degradation of betacatenin. In colon carcinoma cells, loss of APC leads to the accumulation of betacatenin in the nucleus, where it binds to and activates the Tcf-4 transcription factor (reviewed in [1] [2]).

Membrane-tethered Drosophila Armadillo cannot transduce Wingless signal on its own.

Drosophila Armadillo and its vertebrate homolog beta-catenin are key effectors of Wingless/Wnt signaling. In the current model, Wingless/Wnt signal stabilizes Armadillo/beta-catenin, which then accumulates in nuclei and binds TCF/LEF family proteins, forming bipartite transcription factors which activate transcription of Wingless/Wnt responsive genes. This model was recently challenged.

delta-catenin, an adhesive junction-associated protein which promotes cell scattering.

The classical adherens junction that holds epithelial cells together consists of a protein complex in which members of the cadherin family linked to various catenins are the principal components. delta-catenin is a mammalian brain protein in the Armadillo repeat superfamily with sequence similarity to the adherens junction protein p120(ctn). We found that delta-catenin can be immunoprecipitated as a complex with other components of the adherens junction, including cadherin and beta-catenin, from transfected cells and brain.

Drosophila Tcf and Groucho interact to repress Wingless signalling activity.

Wingless/Wnt signalling directs cell-fate choices during embryonic development. Inappropriate reactivation of the pathway causes cancer. In Drosophila, signal transduction from Wingless stabilizes cytosolic Armadillo, which then forms a bipartite transcription factor with the HMG-box protein Drosophila Tcf (dTcf) and activates expression of Wingless-responsive genes.

Roles of Armadillo, a Drosophila catenin, during central nervous system development.

Background: Neural development requires that neurons communicate and co-operate with one another and with other cell types in their environment. Drosophila Armadillo and its vertebrate homolog beta-catenin have dual roles in epithelial cells: transducing signals from the Wingless/Wnt family of proteins and working with cadherins to mediate cell adhesion. Wingless/Wnt signaling also directs certain cell fates in the central nervous system (CNS), and cadherins and catenins are thought to function together during neural development.

Armadillo and dTCF: a marriage made in the nucleus.

Within the past year, Armadillo and beta-catenin's role in transducing the Wingless/Wnt signal has been substantially clarified. It is now clear that Armadillo and beta-catenin bind directly to members of the T-cell factor/lymphoid enhancer factor subfamily of HMG box DNA-binding proteins, forming bipartite transcription factors that regulate Wingless/Wnt responsive genes in both Drosophila and vertebrates. These partners not only play key roles in a variety of cell fate decisions during normal development but, when inappropriately activated, contribute to both colon cancer and melanoma.

Negative regulation of Armadillo, a Wingless effector in Drosophila.

Drosophila Armadillo and its vertebrate homolog beta-catenin play essential roles both in the transduction of Wingless/Wnt cell-cell signals and in the function of cell-cell adherens junctions. Wingless and Wnts direct numerous cell fate choices during development. We generated a mutant protein, Armadillo(S10), with a 54 amino acid deletion in its N-terminal domain.

Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF.

The vertebrate transcription factors TCF (T cell factor) and LEF (lymphocyte enhancer binding factor) interact with beta-catenin and are hypothesized to mediate Wingless/Wnt signaling. We have cloned a maternally expressed Drosophila TCF family member, dTCF. dTCF binds a canonical TCF DNA motif and interacts with the beta-catenin homolog Armadillo.

Drosophila alpha-catenin and E-cadherin bind to distinct regions of Drosophila Armadillo.

Adherens junctions are multiprotein complexes mediating cell-cell adhesion and communication. They are organized around a transmembrane cadherin, which binds a set of cytoplasmic proteins required for adhesion and to link the complex to the actin cytoskeleton. Three components of Drosophila adherens junctions, analogous to those in vertebrates, have been identified: Armadillo (homolog of beta-catenin), Drosophila E-cadherin (DE-cadherin), and alpha-catenin.

Cell-cell signalling: Wingless lands at last.

A novel class of receptor-the Frizzled family-has been identified and the members shown to be receptors for Wingless and its homologs, the Wnts, which mediate key cell-cell interactions during the development of fruitflies and vertebrates, respectively.

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.

Armadillo, the Drosophila homologue of vertebrate beta-catenin, plays a pivotal role both in Wingless signaling and in assembly of adherens junctions. We performed the first in vivo structure-function study of an adherens junction protein, by generating and examining a series of Armadillo mutants in the context of the entire animal. We tested each mutant by assaying its biological function, its ability to bind proteins that normally associate with Armadillo in adherens junctions, its cellular localization, and its pattern of phosphorylation.

Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis.

Morphological and biochemical analyses have identified a set of proteins which together form a structure known as the adherens junction. Elegant experiments in tissue culture support the idea that adherens junctions play a key role in cell-cell adhesion and in organizing cells into epithelia. During normal embryonic development, cells quickly organize epithelia; these epithelial cells participate in many of the key morphogenetic movements of gastrulation.

Localization and possible functions of Drosophila septins.

The septins are a family of homologous proteins that were originally identified in Saccharomyces cerevisiae, where they are associated with the "neck filaments" and are involved in cytokinesis and other aspects of the organization of the cell surface. We report here the identification of Sep1, a Drosophila melanogaster septin, based on its homology to the yeast septins. The predicted Sep1 amino acid sequence is 35-42% identical to the known S.

extradenticle determines segmental identities throughout Drosophila development.

extradenticle (exd) and the homeotic selector proteins together establish segmental identities by coordinately regulating the expression of downstream target genes. The inappropriate expression of these targets in exd mutant embryos results in homeotic transformations and aberrant morphogenesis. Here we examine the role of exd in adult development by using genetic mosaics and a hypomorphic exd allele caused by a point mutation in the homeodomain.

Cell adhesion and signal transduction: the Armadillo connection.

The products of the Drosophila segment polarity gene armadillo and its vertebrate homologue beta-catenin are components of the signal transduction pathway for Wingless/Wnt-1; this signal regulates cell-fate choices in embryos of the fruit fly Drosophila and vertebrates. Armadillo/beta-catenin is also a component of cell-cell adherens junctions in epithelia. How can these two seemingly distinct roles be reconciled? Evidence suggests that Armadillo has distinct functions: one in the adherens junction and one or more in the cytoplasm.

Not just glue: cell-cell junctions as cellular signaling centers.

Proper cell-cell adhesion and communication are essential for normal development and are often perturbed during tumor formation. We have come to realize that cell-cell junctions not only mediate intercellular adhesion, but also serve as organizing centers for specific cell-cell signaling pathways. The characterization of protein components of adhesive and tight/septate junctions in vertebrates and Drosophila is reviewed, and their roles in adhesion and signaling discussed.

Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase.

The Drosophila segment polarity gene product Armadillo provides a link between two seemingly separate processes, regulation of segmental pattern by the Wingless intercellular signal and the function of cell-cell adherens junctions. armadillo was originally identified because of its segment polarity phenotype but subsequently was found to be the homolog of the vertebrate adherens junction protein beta-catenin. We examined the nature of the post-translational modification of Armadillo and its possible role in regulating Armadillo function.