A role for the Drosophila segment polarity gene armadillo in cell adhesion and cytoskeletal integrity during oogenesis

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1191-1207 ◽  
Author(s):  
M. Peifer ◽  
S. Orsulic ◽  
D. Sweeton ◽  
E. Wieschaus
Keyword(s):  
Cell Adhesion ◽  
Germ Line ◽  
Adherens Junctions ◽  
Beta Catenin ◽  
Cell Adhesive ◽  
Segment Polarity ◽  
Drosophila Ovary ◽  
Segment Polarity Gene ◽  
Polarity Gene ◽  
Cell Cell

The epithelial sheet is a structural unit common to many tissues. Its organization appears to depend on the function of the multi-protein complexes that form adherens junctions. Elegant cell biological experiments have provided support for hypotheses explaining the function of adherens junctions and of their components. These systems, however, lack the ability to test function within an entire organism during development. The realization that the product of the Drosophila segment polarity gene armadillo is related to the vertebrate adhesive junction components plakoglobin and beta-catenin led to the suggestion that armadillo might provide a genetic handle to study adhesive junction structure and function. An examination of the potential function of Armadillo in cell-cell adhesive junctions was initiated using the Drosophila ovary as the model system. We examined the distribution of Armadillo in the Drosophila ovary and demonstrated that this localization often parallels the location of cell-cell adhesive junctions. The consequences of removing armadillo function from the germ-line cells of the ovary were also examined. Germ-line armadillo mutations appear to disrupt processes requiring cell adhesion and integrity of the actin cytoskeleton, consistent with a role for Armadillo in cell-cell adhesive junctions. We have also used armadillo mutations to examine the effects on ovarian development of altering the stereotyped cell arrangements of the ovary. The implications of these results for the role of adhesive junctions during development are discussed.

scholarly journals The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties.

1992 ◽  
Vol 118 (3) ◽  
pp. 681-691 ◽  
Author(s):  
M Peifer ◽  
P D McCrea ◽  
K J Green ◽  
E Wieschaus ◽  
B M Gumbiner
Keyword(s):  
Sequence Similarity ◽  
Intracellular Localization ◽  
Amino Acid Sequence Similarity ◽  
Beta Catenin ◽  
Cell Adhesive ◽  
Segment Polarity ◽  
Segment Polarity Gene ◽  
Polarity Gene ◽  
E Cadherin ◽  
Cell Cell

Three proteins identified by quite different criteria in three different systems, the Drosophila segment polarity gene armadillo, the human desmosomal protein plakoglobin, and the Xenopus E-cadherin-associated protein beta-catenin, share amino acid sequence similarity. These findings raise questions about the relationship among the three molecules and their roles in different cell-cell adhesive junctions. We have found that antibodies against the Drosophila segment polarity gene armadillo cross react with a conserved vertebrate protein. This protein is membrane associated, probably via its interaction with a cadherin-like molecule. This cross-reacting protein is the cadherin-associated protein beta-catenin. Using anti-armadillo and antiplakoglobin antibodies, it was shown that beta-catenin and plakoglobin are distinct molecules, which can coexist in the same cell type. Plakoglobin interacts with the desmosomal glycoprotein desmoglein I, and weakly with E-cadherin. Although beta-catenin interacts tightly with E-cadherin, it does not seem to be associated with either desmoglein I or with isolated desmosomes. Anti-armadillo antibodies have been further used to determine the intracellular localization of beta-catenin, and to examine its tissue distribution. The implications of these results for the structure and function of different cell-cell adhesive junctions are discussed.

scholarly journals Induction of a secondary body axis in Xenopus by antibodies to beta-catenin.

1993 ◽  
Vol 123 (2) ◽  
pp. 477-484 ◽  
Author(s):  
P D McCrea ◽  
W M Brieher ◽  
B M Gumbiner
Keyword(s):  
Cell Adhesion ◽  
The Body ◽  
Body Axis ◽  
Beta Catenin ◽  
Gene Products ◽  
Embryonic Patterning ◽  
Xenopus Embryos ◽  
Segment Polarity ◽  
Segment Polarity Gene ◽  
Polarity Gene

We have obtained evidence that a known intracellular component of the cadherin cell-cell adhesion machinery, beta-catenin, contributes to the development of the body axis in the frog Xenopus laevis. Vertebrate beta-catenin is homologous to the Drosophila segment polarity gene product armadillo, and to vertebrate plakoglobin (McCrea, P. D., C. W. Turck, and B. Gumbiner. 1991. Science (Wash. DC). 254: 1359-1361.). Beta-Catenin was found present in all Xenopus embryonic stages examined, and associated with C-cadherin, the major cadherin present in early Xenopus embryos. To test beta-catenin's function, affinity purified Fab fragments were injected into ventral blastomeres of developing four-cell Xenopus embryos. A dramatic phenotype, the duplication of the dorsoanterior embryonic axis, was observed. Furthermore, Fab injections were capable of rescuing dorsal features in UV-ventralized embryos. Similar phenotypes have been observed in misexpression studies of the Wnt and other gene products, suggesting that beta-catenin participates in a signaling pathway which specifies embryonic patterning.

scholarly journals Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin

1994 ◽  
Vol 124 (5) ◽  
pp. 729-741 ◽  
Author(s):  
L Hinck ◽  
WJ Nelson ◽  
J Papkoff
Keyword(s):  
Cell Adhesion ◽  
Mammalian Cells ◽  
Signal Transduction Pathway ◽  
Beta Catenin ◽  
Adhesion Protein ◽  
Calcium Dependent ◽  
Cell Adhesion Protein ◽  
Segment Polarity ◽  
Dependent Cell ◽  
Cell Cell

Wnt-1 homologs have been identified in invertebrates and vertebrates and play important roles in cellular differentiation and organization. In Drosophila, the products of the segment polarity genes wingless (the Wnt-1 homolog) and armadillo participate in a signal transduction pathway important for cellular boundary formation in embryonic development, but functional interactions between the proteins are unknown. We have examined Wnt-1 function in mammalian cells in which armadillo (beta-catenin and plakoglobin) is known to bind to and regulate cadherin cell adhesion proteins. We show that Wnt-1 expression results in the accumulation of beta-catenin and plakoglobin. In addition, binding of beta-catenin to the cell adhesion protein, cadherin, is stabilized, resulting in a concomitant increase in the strength of calcium-dependent cell-cell adhesion. Thus, a consequence of the functional interaction between Wnt-1 and armadillo family members is the strengthening of cell-cell adhesion, which may lead to the specification of cellular boundaries.

scholarly journals Different effects of dominant negative mutants of desmocollin and desmoglein on the cell-cell adhesion of keratinocytes

2000 ◽  
Vol 113 (10) ◽  
pp. 1803-1811
Author(s):  
Y. Hanakawa ◽  
M. Amagai ◽  
Y. Shirakata ◽  
K. Sayama ◽  
K. Hashimoto
Keyword(s):  
Cell Adhesion ◽  
Adherens Junctions ◽  
Dominant Negative ◽  
Cell Contact ◽  
Beta Catenin ◽  
Hacat Cells ◽  
Subsequent Formation ◽  
Contact Sites ◽  
E Cadherin ◽  
Cell Cell

Desmosomes contain two types of cadherin: desmocollin (Dsc) and desmoglein (Dsg). In this study, we examined the different roles that Dsc and Dsg play in the formation of desmosomes, by using dominant-negative mutants. We constructed recombinant adenoviruses (Ad) containing truncated mutants of E-cadherin, desmocollin 3a, and desmoglein 3 lacking a large part of their extracellular domains (EcaddeltaEC, Dsc3adeltaEC, Dsg3deltaEC), using the Cre-loxP Ad system to circumvent the problem of the toxicity of the mutants to virus-producing cells. When Dsc3adeltaEC Ad-infected HaCaT cells were cultured with high levels of calcium, E-cadherin and beta-catenin, which are marker molecules for the adherens junction, disappeared from the cell-cell contact sites, and cell-cell adhesion was disrupted. This also occurred in the cells infected with EcaddeltaEC Ad. With Dsg3deltaEC Ad infection, keratin insertion at the cell-cell contact sites was inhibited and desmoplakin, a marker of desmosomes, was stained in perinuclear dots while the adherens junctions remained intact. Dsc3adeltaEC Ad inhibited the induction of adherens junctions and the subsequent formation of desmosomes with the calcium shift, while Dsg3deltaEC Ad only inhibited the formation of desmosomes. To further determine whether Dsc3adeltaEC directly affected adherens junctions, mouse fibroblast L cells transfected with E-cadherin (LEC5) were infected with these mutant Ads. Both Dsc3adeltaEC and EcaddeltaEC inhibited the cell-cell adhesion of LEC5 cells, as determined by the cell aggregation assay, while Dsg3deltaEC did not. These results indicate that the dominant negative effects of Dsg3deltaEC were restricted to desmosomes, while those of Dsc3adeltaEC were observed in both desmosomes and adherens junctions. Furthermore, the cytoplasmic domain of Dsc3adeltaEC coprecipitated both plakoglobin and beta-catenin in HaCaT cells. In addition, beta-catenin was found to bind the endogenous Dsc in HaCaT cells. These findings lead us to speculate that Dsc interacts with components of the adherens junctions through beta-catenin, and plays a role in nucleating desmosomes after the adherens junctions have been established.

The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction

1993 ◽  
Vol 105 (4) ◽  
pp. 993-1000 ◽  
Author(s):  
M. Peifer
Keyword(s):  
Sequence Similarity ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Beta Catenin ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
Drosophila Homolog ◽  
Segment Polarity ◽  
Associated Proteins ◽  
Segment Polarity Gene

Sequence similarity between the Drosophila segment polarity protein Armadillo and the vertebrate adherens junction protein beta-catenin raised the possibility that adherens junctions function in transduction of intercellular signals like that mediated by Wingless/Wnt-1. To substantiate the sequence similarity, properties of Armadillo were evaluated for consistency with a junctional role. Armadillo is part of a membrane-associated complex. This complex includes Armadillo, a glycoprotein similar in size to vertebrate cadherins, and the Drosophila homolog of alpha-catenin. Armadillo co-localizes with junctions that resemble vertebrate adherens junctions in morphology and position. These results suggest that Drosophila and vertebrate adherens junctions are structurally similar, validating use of Armadillo and its associated proteins as a model for vertebrate adherens junctions.

scholarly journals p120, a p120-related protein (p100), and the cadherin/catenin complex.

1995 ◽  
Vol 130 (2) ◽  
pp. 369-381 ◽  
Author(s):  
J M Staddon ◽  
C Smales ◽  
C Schulze ◽  
F S Esch ◽  
L L Rubin
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cells ◽  
Mdck Cells ◽  
Peptide Sequencing ◽  
Beta Catenin ◽  
Related Protein ◽  
P120 Catenin ◽  
Tissue Sections ◽  
Segment Polarity ◽  
Cell Cell

Cadherins and catenins play an important role in cell-cell adhesion. Two of the catenins, beta and gamma, are members of a group of proteins that contains a repeating amino acid motif originally described for the Drosophila segment polarity gene armadillo. Another member of this group is a 120-kD protein termed p120, originally identified as a substrate of the tyrosine kinase pp60src. In this paper, we show that endothelial and epithelial cells express p120 and p100, a 100-kD, p120-related protein. Peptide sequencing of p100 establishes it as highly related to p120. p120 and p100 both appear associated with the cadherin/catenin complex, but independent p120/catenin and p100/catenin complexes can be isolated. This association is shown by coimmunoprecipitation of cadherins and catenins with an anti-p120/p100 antibody, and of p120/p100 with cadherin or catenin antibodies. Immunocytochemical analysis with a p120-specific antibody reveals junctional colocalization of p120 and beta-catenin in epithelial cells. Catenins and p120/p100 also colocalize in endothelial and epithelial cells in culture and in tissue sections. The cellular content of p120/p100 and beta-catenin is similar in MDCK cells, but only approximately 20% of the p120/p100 pool associates with the cadherin/catenin complex. Our data provide further evidence for interactions among the different arm proteins and suggest that p120/p100 may participate in regulating the function of cadherins and, thereby, other processes influenced by cell-cell adhesion.

Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila

Development ◽  
1992 ◽  
Vol 115 (4) ◽  
pp. 957-971 ◽  
Author(s):  
J. Mohler ◽  
K. Vani
Keyword(s):  
Transmembrane Protein ◽  
Cell Communication ◽  
Protein Product ◽  
Drosophila Embryo ◽  
Molecular Organization ◽  
Posterior Portion ◽  
Segment Polarity ◽  
Segment Polarity Gene ◽  
Polarity Gene ◽  
Cell Cell

hedgehog is a segment polarity gene necessary to maintain the proper organization of each segment of the Drosophila embryo. We have identified the physical location of a number of rearrangement breakpoints associated with hedgehog mutations. The corresponding hh RNA is expressed in a series of segmental stripes starting at cellular blastoderm in the posterior portion of each segment. This RNA is localized predominantly within nuclei until stage 10, when the localization becomes primarily cytoplasmic. Expression of hh RNA in the posterior compartment is independent of most other segment polarity genes, including en, until the late extended germ-band stage (stage 11). Sequence analysis of the hedgehog locus suggests the protein product is a transmembrane protein, which may, therefore, be directly involved in cell-cell communication.

Structure and expression of Hedgehog, a Drosophila segment-polarity gene required for cell-cell communication

Gene ◽  
1993 ◽  
Vol 124 (2) ◽  
pp. 183-189 ◽  
Author(s):  
Tashiro Shigeki ◽  
Michiue Tatsuo ◽  
Higashijima Shin-ichi ◽  
Zenno Shuhei ◽  
Ishimaru Satoshi ◽  
...  
Keyword(s):  
Cell Communication ◽  
Segment Polarity ◽  
Segment Polarity Gene ◽  
Polarity Gene ◽  
Cell Cell
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