ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120(ctn) in E-cadherin complexes

2000 ◽  
Vol 113 (8) ◽  
pp. 1481-1490 ◽  
Author(s):  
D.J. Mariner ◽  
J. Wang ◽  
A.B. Reynolds
Keyword(s):  
Nuclear Translocation ◽  
Adherens Junction ◽  
Cell Types ◽  
Beta Catenin ◽  
Amino Terminal ◽  
Dual Localization ◽  
Preferential Localization ◽  
Repeat Domain ◽  
Armadillo Repeat ◽  
E Cadherin

ARVCF is a novel Armadillo repeat domain protein that is closely related to the catenin p120(ctn). Using new ARVCF monoclonal antibodies, we have found that ARVCF associates with E-cadherin and competes with p120 for interaction with the E-cadherin juxtamembrane domain. ARVCF also localized to the nucleus in some cell types, however, and was significantly more nucleophilic than p120. Surprisingly, despite apparently ubiquitous expression, ARVCF was at least tenfold less abundant than p120 in a wide variety of cell types, and was difficult to detect by immunofluorescence unless overexpressed. Consequently, it is not likely to be abundant enough in adult tissues to functionally compete with p120. ARVCF also completely lacked the ability to induce the cell-branching phenotype associated with overexpression of p120. Expression of ARVCF/p120 chimeras confirmed previous results indicating that the branching activity of p120 maps to its Armadillo repeat domain. Surprisingly, the preferential localization of ARVCF to the nucleus required sequences in the amino-terminal end of ARVCF, suggesting that the sequences directing nuclear translocation of ARVCF are distinct from the predicted bipartite nuclear localization signal located between repeats 6 and 7. The dual localization of ARVCF to junctions and to nuclei suggests activities in different cellular compartments, as is the case for several other Armadillo repeat proteins including beta-catenin, p120 and the plakophilins.

scholarly journals Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling.

1995 ◽  
Vol 128 (5) ◽  
pp. 959-968 ◽  
Author(s):  
N Funayama ◽  
F Fagotto ◽  
P McCrea ◽  
B M Gumbiner
Keyword(s):  
Cell Adhesion ◽  
Intracellular Signaling ◽  
Ventral Side ◽  
Xenopus Embryo ◽  
Protein Interaction Data ◽  
Beta Catenin ◽  
Repeat Region ◽  
Amino Terminal ◽  
Repeat Domain ◽  
Armadillo Repeat

beta-catenin was identified as a cytoplasmic cadherin-associated protein required for cadherin adhesive function (Nagafuchi, A., and M. Takeichi. 1989. Cell Regul. 1:37-44; Ozawa, M., H. Baribault, and R. Kemler. 1989. EMBO [Eur. Mol. Biol. Organ.] J. 8:1711-1717). Subsequently, it was found to be the vertebrate homologue of the Drosophila segment polarity gene product Armadillo (McCrea, P. D., C. W. Turck, and B. Gumbiner. 1991. Science [Wash. DC]. 254:1359-1361; Peifer, M., and E. Wieschaus. 1990. Cell. 63:1167-1178). Also, antibody perturbation experiments implicated beta-catenin in axial patterning of the early Xenopus embryo (McCrea, P. D., W. M. Brieher, and B. M. Gumbiner. 1993. J. Cell Biol. 123:477-484). Here we report that overexpression of beta-catenin in the ventral side of the early Xenopus embryo, by injection of synthetic beta-catenin mRNA, induces the formation of a complete secondary body axis. Furthermore, an analysis of beta-catenin deletion constructs demonstrates that the internal armadillo repeat region is both necessary and sufficient to induce axis duplication. This region interacts with C-cadherin and with the APC tumor suppressor protein, but not with alpha-catenin, that requires the amino-terminal region of beta-catenin to bind to the complex. Since alpha-catenin is required for cadherin-mediated adhesion, the armadillo repeat region alone probably cannot promote cell adhesion, making it unlikely that beta-catenin induces axis duplication by increasing cell adhesion. We propose, rather, that beta-catenin acts in this circumstance as an intracellular signaling molecule. Subcellular fractionation demonstrated that all of the beta-catenin constructs that contain the armadillo repeat domain were present in both the soluble cytosolic and the membrane fraction. Immunofluorescence staining confirmed the plasma membrane and cytoplasmic localization of the constructs containing the armadillo repeat region, but revealed that they also accumulate in the nucleus, especially the construct containing only the armadillo repeat domain. These findings and the beta-catenin protein interaction data offer several intriguing possibilities for the site of action or the protein targets of beta-catenin signaling activity.

scholarly journals P120 regulates beta-catenin nuclear translocation through E-cadherin endocytosis in ventilator-induced lung injury

Oncotarget ◽  
2016 ◽  
Vol 7 (51) ◽  
pp. 83859-83868 ◽  
Author(s):  
Changping Gu ◽  
Chenyang Dai ◽  
Yongtao Sun ◽  
Mengjie Liu ◽  
Yuelan Wang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Nuclear Translocation ◽  
Beta Catenin ◽  
Ventilator Induced Lung Injury ◽  
E Cadherin

scholarly journals The roles of catenins in the cadherin-mediated cell adhesion: functional analysis of E-cadherin-alpha catenin fusion molecules.

1994 ◽  
Vol 127 (1) ◽  
pp. 235-245 ◽  
Author(s):  
A Nagafuchi ◽  
S Ishihara ◽  
S Tsukita
Keyword(s):  
Cell Adhesion ◽  
Cell Movement ◽  
Negative Regulator ◽  
Beta Catenin ◽  
Amino Terminal ◽  
Cytoplasmic Proteins ◽  
The Difference ◽  
Adhesion Activity ◽  
Carboxy Terminal ◽  
E Cadherin

The carboxyl terminus-truncated cadherin (nonfunctional cadherin) has no cell adhesion activity probably because of its failure to associate with cytoplasmic proteins called alpha and beta catenin. To rescue this nonfunctional cadherin as adhesion molecules, we constructed three cDNAs for fusion proteins between nonfunctional E-cadherin and alpha catenin, nE alpha, nE alpha N, and nE alpha C, where the intact, amino-terminal and carboxy-terminal half of alpha catenin, respectively, were directly linked to the nonfunctional E-cadherin, and introduced them into mouse L cells. The subcellular distribution and cell adhesion activity of nE alpha and nE alpha C molecules was similar to those of intact E-cadherin transfectants: they bound to cytoskeletons, were concentrated at cell-cell adhesion sites and showed strong cell adhesion activity. nE alpha N molecules, which also bound to cytoskeletons, showed very poor cell adhesion activity. Taken together, we conclude that in the formation of the cadherin-catenin complex, the mechanical association of alpha catenin, especially its carboxy-terminal half, with E-cadherin is a key step for the cadherin-mediated cell adhesion. Close comparison revealed that the behavior of nE alpha molecules during cytokinesis was quite different from that of intact E-cadherin, and that the intercellular motility, i.e., the cell movement in a confluent sheet, was significantly suppressed in nE alpha transfectants although it was facilitated in E-cadherin transfectants. Considering that nE alpha was not associated with endogenous beta catenin in transfectants, the difference in the nature of cell adhesion between nE alpha and intact E-cadherin transfectants may be explained by the function of beta catenin. The possible functions of beta catenin are discussed with a special reference to its role as a negative regulator for the cadherin-mediated cell adhesion system.

scholarly journals The Function of Plakophilin 1 in Desmosome Assembly and Actin Filament Organization

2000 ◽  
Vol 149 (1) ◽  
pp. 209-222 ◽  
Author(s):  
Mechthild Hatzfeld ◽  
Christof Haffner ◽  
Katrin Schulze ◽  
Ute Vinzens
Keyword(s):  
Dominant Negative ◽  
Binding Partners ◽  
Yeast Two Hybrid System ◽  
Head Domain ◽  
Dual Localization ◽  
Repeat Domain ◽  
Armadillo Repeat ◽  
Two Hybrid ◽  
Negative Phenotype

Plakophilin 1, a member of the armadillo multigene family, is a protein with dual localization in the nucleus and in desmosomes. To elucidate its role in desmosome assembly and regulation, we have analyzed its localization and binding partners in vivo. When overexpressed in HaCaT keratinocytes, plakophilin 1 localized to the nucleus and to desmosomes, and dramatically enhanced the recruitment of desmosomal proteins to the plasma membrane. This effect was mediated by plakophilin 1's head domain, which interacted with desmoglein 1, desmoplakin, and keratins in the yeast two-hybrid system. Overexpression of the armadillo repeat domain induced a striking dominant negative phenotype with the formation of filopodia and long cellular protrusions, where plakophilin 1 colocalized with actin filaments. This phenotype was strictly dependent on a conserved motif in the center of the armadillo repeat domain. Our results demonstrate that plakophilin 1 contains two functionally distinct domains: the head domain, which could play a role in organizing the desmosomal plaque in suprabasal cells, and the armadillo repeat domain, which might be involved in regulating the dynamics of the actin cytoskeleton.

PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin

1999 ◽  
Vol 112 (18) ◽  
pp. 3005-3014 ◽  
Author(s):  
N. Ilan ◽  
S. Mahooti ◽  
D.L. Rimm ◽  
J.A. Madri
Keyword(s):  
Endothelial Cell ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Nuclear Translocation ◽  
Adherens Junction ◽  
Cell Contact ◽  
Beta Catenin ◽  
Dependent Manner

Catenins function as regulators of cellular signaling events in addition to their previously documented roles in adherens junction formation and function. Evidence to date suggests that beta and gamma catenins can act as signaling molecules, bind transcriptional factors and translocate to the nucleus. Beta- and gamma-catenin are also major substrates for protein tyrosine kinases, and tyrosine phosphorylation of junctional proteins is correlated with decreased adhesiveness. One way in which catenin functions are modulated is by dynamic incorporation into junctional complexes which controls, in part, the cytoplasmic levels of catenins. Here we show that: (1) vascular endothelial growth factor (VEGF) induces beta-catenin tyrosine phosphorylation in a time-, and dose-dependent manner and that VEGF receptors co-localize to areas of endothelial cell-cell contact in vitro and in vivo. (2) Platelet-endothelial cell adhesion molecule (PECAM)-1 can function as a reservoir for, and modulator of, tyrosine phosphorylated beta-catenin. (3) PECAM-1 can prevent beta-catenin nuclear translocation in transfected SW480 colon carcinoma cells. We suggest that PECAM-1 may play a role in modulating beta-catenin tyrosine phosphorylation levels, localization and signaling and by doing so, functions as an important modulator of the endothelium.

Caspase‐mediated cleavage of APC results in an amino‐terminal fragment with an intact armadillo repeat domain

1999 ◽  
Vol 13 (2) ◽  
pp. 339-346 ◽  
Author(s):  
STEPHANIE JOHNSON WEBB ◽  
DONALD NICHOLSON ◽  
VIVIEN J. BUBB ◽  
ANDREW H. WYLLIE
Keyword(s):  
Amino Terminal ◽  
Terminal Fragment ◽  
Repeat Domain ◽  
Armadillo Repeat ◽  
Amino Terminal Fragment

scholarly journals N-Terminal 1–54 Amino Acid Sequence and Armadillo Repeat Domain Are Indispensable for P120-Catenin Isoform 1A in Regulating E-Cadherin

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37008 ◽  
Author(s):  
Juanhan Yu ◽  
Yuan Miao ◽  
Hongtao Xu ◽  
Yang Liu ◽  
Guiyang Jiang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
P120 Catenin ◽  
Repeat Domain ◽  
Armadillo Repeat ◽  
E Cadherin

scholarly journals beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex.

1996 ◽  
Vol 134 (5) ◽  
pp. 1271-1281 ◽  
Author(s):  
Y S Tao ◽  
R A Edwards ◽  
B Tubb ◽  
S Wang ◽  
J Bryan ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Beta Catenin ◽  
Cortical Actin ◽  
Repeat Domain ◽  
Domain Mapping ◽  
Armadillo Repeat ◽  
Leading Edges ◽  
Cell Cell

Catenins were first characterized as linking the cytoplasmic domains of cadherin cell-cell adhesion molecules to the cortical actin cytoskeleton. In addition to their essential role in modulating cadherin adhesivity, catenins have more recently been indicated to participate in cell and developmental signaling pathways. beta-Catenin, for example, associates directly with at least two receptor tyrosine kinases and transduces developmental signals within the Wnt pathway. Catenins also complex with the tumor suppressor protein adenomatous polyposis coli (APC), which appears to have a role in regulating cell proliferation. We have used the yeast two-hybrid method to reveal that fascin, a bundler of actin filaments, binds to beta-catenin's central Armadillo repeat domain. Western blotting of immunoprecipitates from cell line and mouse and rat brain extracts indicate that this interaction exists in vivo. Fascin and beta-catenin's association was further substantiated in vitro using purified proteins isolated from recombinant bacterial and baculoviral sources. Immunoprecipitation analysis indicates that fascin additionally binds to plakoglobin, which is highly homologous to beta-catenin but not to p120cas, a newly described catenin which contains a more divergent Armadillo-repeat domain. Immunoprecipitation, in vitro competition, and domain-mapping experiments demonstrate that fascin and E-cadherin utilize a similar binding site within beta-catenin, such that they form mutually exclusive complexes with beta-catenin. Immunofluorescence microscopy reveals that fascin and beta-catenin colocalize at cell-cell borders and dynamic cell leading edges of epithelial and endothelial cells. In addition to cell-cell borders, cadherins were unexpectedly observed to colocalize with fascin and beta-catenin at cell leading edges. It is conceivable that beta-catenin participates in modulating cytoskeletal dynamics in association with the microfilament-bundling protein fascin, perhaps in a coordinate manner with its functions in cadherin and APC complexes.

scholarly journals α-Catenin contributes to the strength of E-cadherin–p120 interactions

2011 ◽  
Vol 22 (22) ◽  
pp. 4247-4255 ◽  
Author(s):  
Regina B. Troyanovsky ◽  
Jörg Klingelhöfer ◽  
Sergey M. Troyanovsky
Keyword(s):  
Alternative Splicing ◽  
Amino Acid ◽  
Cross Linking ◽  
Full Size ◽  
Binding Strength ◽  
Amino Terminal ◽  
Large Loop ◽  
Repeat Domain ◽  
Surface Examination ◽  
E Cadherin

Cadherin–catenin interactions play an important role in cadherin-mediated adhesion. Here we present strong evidence that in the cadherin–catenin complex α-catenin contributes to the binding strength of another catenin, p120, to the same complex. Specifically, we found that a β-catenin–uncoupled cadherin mutant interacts much more weakly with p120 than its full-size counterpart and that it is rapidly endocytosed from the surface of A-431 cells. We also showed that p120 overexpression stabilizes this mutant on the cell surface. Examination of the α-catenin–deficient MDA-MB-468 cells and their derivates in which α-catenin was reintroduced showed that α-catenin reinforces E-cadherin–p120 association. Finally, a cross-linking analysis of the cadherin–catenin complex indicated that a large loop located in the middle of the p120 arm-repeat domain is in close spatial vicinity to the amino-terminal VH1 domain of α-catenin. The six amino acid–long extension of this loop, caused by an alternative splicing, weakens p120 binding to cadherin. The data suggest that α-catenin–p120 contact within the cadherin–catenin complex can regulate cadherin trafficking.

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