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Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Wnt genes encode secreted glycoproteins used in intercellular communication at multiple steps during development. Signalling by Wingless, the Drosophila Wnt-1 homologue, requires the activity of Armadillo, the homologue of vertebrate beta-catenin, which is a component of the cadherin/catenin complex at adherens junctions. The genetic link between wingless and armadillo suggests that cell fate specification and cell-cell adhesion might be controlled concurrently. For instance, in one extreme view, Wingless could specify cell fate entirely by modulating cell adhesion. Alternatively, it might signal independently of adherens junctions. To distinguish between these alternatives, we have expressed two polypeptides that have opposite effects on cadherin-dependent adhesion: full-length Drosophila E-cadherin and a dominant-negative truncated form. We found that overexpression of either construct mimics wingless phenotypes, thereby uncoupling changes in adhesion from signalling effects. We demonstrate that both constructs titrate Armadillo from a 'signalling' pool which is functionally distinct from the junctional pool.
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PMID:Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. 885 39

Invasion is the cause of cancer malignancy. Invasion results from the cross-talk between cancer cells and host cells, building molecular invasion-promoter and invasion-suppressor complexes. The E-cadherin/catenin invasion-suppressor complex is regulated multifactorially, at multiple levels and sometimes in a reversible way. Mutations in the E-cadherin gene combined with loss of the wild type allele, causing irreversible downregulation, has been demonstrated only in a minority of human cancers. Posttranslational and reversible downregulation has been ascribed to tyrosine phosphorylation of beta-catenin. Phosphorylation is also implicated in transmembrane receptor signal transduction through the E-cadherin/catenin complex. E-cadherin interacts with E-cadherin on another cell through a dimeric adhesion zipper, involving the histidine-alanine-valine (HAV) sequence of the first extracellular domains. This is the major extracellular like of the E-cadherin/catenin complex, though not the only one. Intracellularly, the list of proteins that bind to or signal through the complex or through one or more of its elements is steadily growing. Extrinsic factors may influence the complex. At least in vitro, insulin-like growth factor-I, retinoic acid, tangeretin and tamoxifen were shown to upregulate the functions of the E-cadherin/catenin complex including inhibition of invasion.
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PMID:Regulation of the invasion suppressor function of the cadherin/catenin complex. 888 Aug 70

Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE-cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE-cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen-reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE-cadherin distribution was affected by PMN adhesion to the vessel wall in vivo too. This work suggests that PMN adhesion could trigger intracellular signals in EC that possibly regulate VE-cadherin /catenin complex disorganization. This effect could increase EC permeability and facilitate PMN transmigration during the acute inflammatory reaction.
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PMID:Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions. 889 5

Molecular mechanisms linking pre- and postsynaptic membranes at the interneuronal synapses are little known. We tested the cadherin adhesion system for its localization in synapses of mouse and chick brains. We found that two classes of cadherin-associated proteins, alpha N- and beta-catenin, are broadly distributed in adult brains, colocalizing with a synaptic marker, synaptophysin. At the ultrastructural level, these proteins were localized in synaptic junctions of various types, forming a symmetrical adhesion structure. These structures sharply bordered the transmitter release sites associated with synaptic vesicles, although their segregation was less clear in certain types of synapses. N-cadherin was also localized at a similar site of synaptic junctions but in restricted brain nuclei. In developing synapses, the catenin-bearing contacts dominated their junctional structures. These findings demonstrate that interneuronal synaptic junctions comprise two subdomains, transmitter release zone and catenin-based adherens junction. The catenins localized in these junctions are likely associated with certain cadherin molecules including N-cadherin, and the cadherin/ catenin complex may play a critical role in the formation or maintenance of synaptic junctions.
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PMID:The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. 890 49

Plakoglobin is the only component common to both the desmosomal plaque and the cadherin-catenin cell adhesion complex in the adherens junction. It is highly homologous to vertebrate beta-catenin and to Drosophila armadillo protein and may-like these proteins-be also involved in signaling pathways. To analyze the role of plakoglobin during mouse development we inactivated the plakoglobin gene by homologous recombination in embryonic stem cells and generated transgenic mice. Plakoglobin null-mutant embryos died from Embryonic Day 10.5 onward, due to severe heart defects. Some mutant embryos developed further, especially on a C57BL/6 genetic background, and died around birth, presumably due to cardiac dysfunction, and with skin blistering and subcorneal acantholysis. Ultrastructural analysis revealed that here desmosomes were greatly reduced in number and structurally altered. Thus, using reversed genetics we demonstrate that plakoglobin is an essential structural component for desmosome function. The skin phenotype in plakoglobin-deficient mice is reminiscent of the human blistering disease, epidermolytic hyperkeratosis.
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PMID:Embryonic heart and skin defects in mice lacking plakoglobin. 895 45

Cadherins are Ca2(+)-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the histo-architecture. Using cultured human leukemia cell lines (adult T cell leukemia and thymus-derived lymphoma cell lines), we obtained evidence that cadherins and catenins are expressed in these cell lines but not in normal leukocytes. Immunoblot analysis of cells using a pan-cadherin serum, directed against the conserved carboxyl-terminus of cadherins, revealed a major band of 130 kDa and a minor one of 135 kDa. The 130 kDa cadherin was also recognized by anti-N-cadherin antibodies. A human N-cadherin cDNA probe hybridized to a 4.3 kb mRNA isolated from cells immunologically positive for N-cadherin. Sequencing of the cDNA fragments isolated from the cells revealed a N-cadherin sequence. Cell surface expression of N-cadherin was confirmed by indirect immunofluorescence staining of the cells. Immunoblot and Northern blot analyses also revealed the presence of alpha-catenin, beta-catenin, and gamma-catenin (plakoglobin) in these cell lines. Immunoprecipitation with anti-N-cadherin antibodies and subsequent immunoblot analysis with anti-catenin antibodies revealed that N-cadherin is associated with alpha- and beta-catenins, a prerequisite for cadherins to be functional. These results suggest an important role of the cadherin-catenin complexes in the behavior of the leukemia cells.
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PMID:Expression of cadherin-catenin complexes in human leukemia cell lines. 898 73

Epithelial cell-cell adhesion requires interactions between opposing extracellular domains of E-cadherin, and among the cytoplasmic domain of E-cadherin, catenins, and actin cytoskeleton. Little is known about how the cadherin-catenin-actin complex is assembled upon cell-cell contact, or how these complexes initiate and strengthen adhesion. We have used time-lapse differential interference contrast (DIC) imaging to observe the development of cell-cell contacts, and quantitative retrospective immunocytochemistry to measure recruitment of proteins to those contacts. We show that E-cadherin, alpha-catenin, and beta-catenin, but not plakoglobin, coassemble into Triton X-100 insoluble (TX-insoluble) structures at cell-cell contacts with kinetics similar to those for strengthening of E-cadherin-mediated cell adhesion (Angres, B., A. Barth, and W.J. Nelson. 1996. J. Cell Biol. 134:549-557). TX-insoluble E-cadherin, alpha-catenin, and beta-catenin colocalize along cell-cell contacts in spatially discrete micro-domains which we designate "puncta," and the relative amounts of each protein in each punctum increase proportionally. As the length of the contact increases, the number of puncta increases proportionally along the contact and each punctum is associated with a bundle of actin filaments. These results indicate that localized clustering of E-cadherin/catenin complexes into puncta and their association with actin is involved in initiating cell contacts. Subsequently, the spatial ordering of additional puncta along the contact may be involved in zippering membranes together, resulting in rapid strengthening of adhesion.
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PMID:Quantitative analysis of cadherin-catenin-actin reorganization during development of cell-cell adhesion. 899 Nov

Cell adhesion molecules are not only required for maintenance of tissue integrity, but also regulate many aspects of cell behaviour, including growth and differentiation. While the regulatory functions of integrin extracellular matrix receptors in keratinocytes are well established, such functions have not been investigated for the primary receptors that mediate keratinocyte intercellular adhesion, the cadherins. To examine cadherin function in normal human epidermal keratinocytes we used a retroviral vector to introduce a dominant negative E-cadherin mutant, consisting of the extracellular domain of H-2Kd and the transmembrane and cytoplasmic domains of E-cadherin. As a control a vector containing the same construct, but with the catenin binding site destroyed, was prepared. High levels of expression of the constructs were achieved; the dominant negative mutant, but not the control, formed complexes with alpha-, beta- and gamma-catenin. In cells expressing the dominant negative mutant there was a 5-fold decrease in the level of endogenous cadherins and a 3-fold increase in the level of beta-catenin. Cell-cell adhesion and stratification were inhibited by the dominant negative mutant and desmosome formation was reduced. Expression of the mutant resulted in reduced levels of the alpha 2 beta 1 and alpha 3 beta 1 integrins and increased cell motility, providing further evidence for cross-talk between cadherins and the beta 1 integrins. In view of the widely documented loss of E-cadherin in keratinocyte tumours it was surprising that the dominant negative mutant had an inhibitory effect on keratinocyte proliferation and stimulated terminal differentiation even under conditions in which intercellular adhesion was prevented. These results establish a role for cadherins in regulating keratinocyte growth and differentiation and raise interesting questions as to the relative importance of cell adhesion-dependent and -independent mechanisms.
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PMID:Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes. 900 36

Cadherins are transmembrane receptors with an extracellular domain that participates in homophilic cell to cell adhesion and a cytoplasmic domain that associates with proteins called catenins. Cadherin-mediated adhesion as well as adhesion-independent functions for catenins play important roles in differentiation, development, and malignant transformation. Mechanisms that regulate steady-state catenin levels and cadherin-catenin complex stability are poorly understood, but activities of both the Wnt-1 proto-oncogene and tyrosine kinases are implicated. Here I define, at the biochemical level, distinct mechanisms that modulate steady-state catenin levels. Increased cadherin expression, providing more catenin binding sites, leads to selective stabilization of the cadherin-associated population of alpha- and beta-catenin, but not p120(cas). In contrast, expression of Wnt-1 leads primarily to increased stability of the uncomplexed pool of beta-catenin without effect on p120(cas). Significantly, the Wnt-1-induced stabilization of uncomplexed beta-catenin is independent of cadherin expression. Transformation by v-Src does not disrupt the catenin-cadherin complex despite the phosphorylation of E-cadherin and beta-catenin on tyrosine. In contrast to the effects of Wnt-1, v-Src does not modulate the uncomplexed population of beta-catenin. p120(cas) is phosphorylated on tyrosine by v-Src, and this is accompanied by a significant decrease in the level of uncomplexed p120(cas) as well as a change in behavior of p120(cas) upon biochemical fractionation. Taken together these data suggest that p120(cas) and beta-catenin are regulated independently.
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PMID:Regulation of complexed and free catenin pools by distinct mechanisms. Differential effects of Wnt-1 and v-Src. 902 Jan 80

beta-Catenin is essential for the function of cadherins, a family of Ca2+-dependent cell-cell adhesion molecules, by linking them to (alpha)-catenin and the actin cytoskeleton. beta-Catenin also binds to adenomatous polyposis coli (APC) protein, a cytosolic protein that is the product of a tumor suppressor gene mutated in colorectal adenomas. We have expressed mutant beta-catenins in MDCK epithelial cells to gain insights into the regulation of beta-catenin distribution between cadherin and APC protein complexes and the functions of these complexes. Full-length beta-catenin, beta-catenin mutant proteins with NH2-terminal deletions before (deltaN90) or after (deltaN131, deltaN151) the alpha-catenin binding site, or a mutant beta-catenin with a COOH-terminal deletion (delta C) were expressed in MDCK cells under the control of the tetracycline-repressible transactivator. All beta-catenin mutant proteins form complexes and colocalize with E-cadherin at cell-cell contacts; deltaN90, but neither deltaN131 nor deltaN151, bind alpha-catenin. However, beta-catenin mutant proteins containing NH2-terminal deletions also colocalize prominently with APC protein in clusters at the tips of plasma membrane protrusions; in contrast, full-length and COOH-terminal-deleted beta-catenin poorly colocalize with APC protein. NH2-terminal deletions result in increased stability of beta-catenin bound to APC protein and E-cadherin, compared with full-length beta-catenin. At low density, MDCK cells expressing NH2-terminal-deleted beta-catenin mutants are dispersed, more fibroblastic in morphology, and less efficient in forming colonies than parental MDCK cells. These results show that the NH2 terminus, but not the COOH terminus of beta-catenin, regulates the dynamics of beta-catenin binding to APC protein and E-cadherin. Changes in beta-catenin binding to cadherin or APC protein, and the ensuing effects on cell morphology and adhesion, are independent of beta-catenin binding to alpha-catenin. These results demonstrate that regulation of beta-catenin binding to E-cadherin and APC protein is important in controlling epithelial cell adhesion.
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PMID:NH2-terminal deletion of beta-catenin results in stable colocalization of mutant beta-catenin with adenomatous polyposis coli protein and altered MDCK cell adhesion. 902 98


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