The p120 catenin family: complex roles in adhesion, signaling and cancer

2000 ◽  
Vol 113 (8) ◽  
pp. 1319-1334 ◽  
Author(s):  
P.Z. Anastasiadis ◽  
A.B. Reynolds
Keyword(s):  
Cell Adhesion ◽  
Biological Function ◽  
Family Members ◽  
Cell Junctions ◽  
Beta Catenin ◽  
Juxtamembrane Domain ◽  
P120 Catenin ◽  
Structural Relationships ◽  
Classical Cadherins ◽  
Cell Cell

p120 catenin (p120) is the prototypic member of a growing subfamily of Armadillo-domain proteins found at cell-cell junctions and in nuclei. In contrast to the functions of the classical catenins (alpha-catenin, beta-catenin, and gamma-catenin/plakoglobin), which have been studied extensively, the first clues to p120's biological function have only recently emerged, and its role remains controversial. Nonetheless, it is now clear that p120 affects cell-cell adhesion through its interaction with the highly conserved juxtamembrane domain of classical cadherins, and is likely to have additional roles in the nucleus. Here, we summarize the data on the potential involvement of p120 both in promotion of and in prevension of adhesion, and propose models that attempt to reconcile some of the disparities in the literature. We also discuss the structural relationships and functions of several known p120 family members, as well as the potential roles of p120 in signaling and cancer.

scholarly journals Selective Uncoupling of P120ctn from E-Cadherin Disrupts Strong Adhesion

2000 ◽  
Vol 148 (1) ◽  
pp. 189-202 ◽  
Author(s):  
Molly A. Thoreson ◽  
Panos Z. Anastasiadis ◽  
Juliet M. Daniel ◽  
Reneé C. Ireton ◽  
Margaret J. Wheelock ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Single Cells ◽  
Subcellular Fractionation ◽  
Juxtamembrane Domain ◽  
Classical Cadherins ◽  
Strong Adhesion ◽  
Direct Binding ◽  
E Cadherin ◽  
Cell Cell

p120ctn is a catenin whose direct binding to the juxtamembrane domain of classical cadherins suggests a role in regulating cell–cell adhesion. The juxtamembrane domain has been implicated in a variety of roles including cadherin clustering, cell motility, and neuronal outgrowth, raising the possibility that p120 mediates these activities. We have generated minimal mutations in this region that uncouple the E-cadherin–p120 interaction, but do not affect interactions with other catenins. By stable transfection into E-cadherin–deficient cell lines, we show that cadherins are both necessary and sufficient for recruitment of p120 to junctions. Detergent-free subcellular fractionation studies indicated that, in contrast to previous reports, the stoichiometry of the interaction is extremely high. Unlike α- and β-catenins, p120 was metabolically stable in cadherin-deficient cells, and was present at high levels in the cytoplasm. Analysis of cells expressing E-cadherin mutant constructs indicated that p120 is required for the E-cadherin–mediated transition from weak to strong adhesion. In aggregation assays, cells expressing p120-uncoupled E-cadherin formed only weak cell aggregates, which immediately dispersed into single cells upon pipetting. As an apparent consequence, the actin cytoskeleton failed to insert properly into peripheral E-cadherin plaques, resulting in the inability to form a continuous circumferential ring around cell colonies. Our data suggest that p120 directly or indirectly regulates the E-cadherin–mediated transition to tight cell–cell adhesion, possibly blocking subsequent events necessary for reorganization of the actin cytoskeleton and compaction.

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.

scholarly journals CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions

2013 ◽  
Vol 203 (6) ◽  
pp. 1043-1061 ◽  
Author(s):  
Marta N. Shahbazi ◽  
Diego Megias ◽  
Carolina Epifano ◽  
Anna Akhmanova ◽  
Gregg G. Gundersen ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adherens Junctions ◽  
Direct Interaction ◽  
P120 Catenin ◽  
Basal Progenitor ◽  
Classical Cadherins ◽  
Functional Implications ◽  
Functional Relevance ◽  
Mouse Keratinocytes ◽  
Cell Cell

Classical cadherins and their connections with microtubules (MTs) are emerging as important determinants of cell adhesion. However, the functional relevance of such interactions and the molecular players that contribute to tissue architecture are still emerging. In this paper, we report that the MT plus end–binding protein CLASP2 localizes to adherens junctions (AJs) via direct interaction with p120-catenin (p120) in primary basal mouse keratinocytes. Reductions in the levels of p120 or CLASP2 decreased the localization of the other protein to cell–cell contacts and altered AJ dynamics and stability. These features were accompanied by decreased MT density and altered MT dynamics at intercellular junction sites. Interestingly, CLASP2 was enriched at the cortex of basal progenitor keratinocytes, in close localization to p120. Our findings suggest the existence of a new mechanism of MT targeting to AJs with potential functional implications in the maintenance of proper cell–cell adhesion in epidermal stem cells.

scholarly journals Stick around: Cell–Cell Adhesion Molecules during Neocortical Development

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 118
Author(s):  
David de Agustín-Durán ◽  
Isabel Mateos-White ◽  
Jaime Fabra-Beser ◽  
Cristina Gil-Sanz
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Neural Cells ◽  
Surface Receptors ◽  
Cellular Processes ◽  
Neocortical Development ◽  
Classical Cadherins ◽  
Adhesive Interactions ◽  
Cell Cell

The neocortex is an exquisitely organized structure achieved through complex cellular processes from the generation of neural cells to their integration into cortical circuits after complex migration processes. During this long journey, neural cells need to establish and release adhesive interactions through cell surface receptors known as cell adhesion molecules (CAMs). Several types of CAMs have been described regulating different aspects of neurodevelopment. Whereas some of them mediate interactions with the extracellular matrix, others allow contact with additional cells. In this review, we will focus on the role of two important families of cell–cell adhesion molecules (C-CAMs), classical cadherins and nectins, as well as in their effectors, in the control of fundamental processes related with corticogenesis, with special attention in the cooperative actions among the two families of C-CAMs.

Long-range and selective autoregulation of cell-cell or cell-matrix adhesions by cadherin or integrin ligands

1998 ◽  
Vol 111 (3) ◽  
pp. 347-357 ◽  
Author(s):  
S. Levenberg ◽  
B.Z. Katz ◽  
K.M. Yamada ◽  
B. Geiger
Keyword(s):  
Cell Surface ◽  
Tyrosine Phosphorylation ◽  
Long Range ◽  
Cell Junctions ◽  
Complete Suppression ◽  
Beta Catenin ◽  
Focal Contact ◽  
Cell Matrix ◽  
Immunofluorescence Labeling ◽  
Cell Cell

In this study we demonstrate that local stimulation of cell surface cadherins or integrins induces a selective enhancement of adherens junction or focal contact assembly, respectively, throughout the cell. N-cadherin transfected CHO cells (CHO-Ncad) were incubated with different ligands including N-cadherin extracellular domain (NEC), anti-N-cadherin antibodies, fibronectin and concanavalin A (ConA), conjugated to synthetic beads. Electron microscopic examination indicated that both cadherin- and integrin-reactive beads bound tightly to the cell surface and were apparently endocytosed after several hours of incubation. The ConA-beads remained largely at the cell surface. Immunofluorescence labeling of the cells with antibodies to different adhesion-associated molecules indicated that both NEC- and anti-N-cadherin-conjugated beads induced a major increase in the level of junction-associated cadherin and beta-catenin labeling and a modest increase in junctional vinculin labeling, compared to untreated cells or cells bound to ConA-beads. FN-conjugated beads, on the other hand, significantly enhanced vinculin labeling at focal contacts and suppressed cadherin and beta-catenin staining in cell-cell junctions. The cadherin-reactive beads specifically stimulated tyrosine phosphorylation at cell-cell junctions, while the FN-beads increased the levels of focal contact-associated phosphotyrosine, as shown by immunofluorescence labeling of the cells for phosphotyrosine. Inhibition of this phosphorylation by genistein resulted in a complete suppression of the effects of both types of beads. These findings indicate that specific cadherin- and integrin-mediated surface interactions can trigger positively cooperative long-range signaling events which lead to the selective assembly of cell-cell or cell-matrix adhesions, and that these signals involve tyrosine phosphorylation.

Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells

1997 ◽  
Vol 110 (17) ◽  
pp. 2065-2077 ◽  
Author(s):  
M.G. Lampugnani ◽  
M. Corada ◽  
P. Andriopoulou ◽  
S. Esser ◽  
W. Risau ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Phosphorylation ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Molecular Organization ◽  
Beta Catenin ◽  
Cell Contacts ◽  
Cell Type Specific ◽  
Dynamic Structures ◽  
Cell Cell

In src- and ras-transformed cells, tyrosine phosphorylation of adherens junction (AJ) components is related to impairment of cell-cell adhesion. In this paper we report that in human endothelial cells (EC), tyrosine phosphorylation of AJ can be a physiological process regulated by cell density. Immunofluorescence analysis revealed that a phosphotyrosine (P-tyr) antibody could stain cell-cell junctions only in sparse or loosely confluent EC, while the staining was markedly reduced in tightly confluent cultures. This process was reversible, since on artificial wounding of EC monolayers, the cells at the migrating front reacquired P-tyr labelling at cell contacts. In EC, the major cadherin at intercellular AJ is the cell-type-specific VE-cadherin. We therefore analyzed whether this molecule was at least in part responsible for the changes in P-tyr content at cell junctions. Tyrosine phosphorylation of VE-cadherin, beta-catenin and p120, occurred in looser AJ, i.e. in recently confluent cells, and was notably reduced in tightly confluent cultures. Changes in P-tyr content paralleled changes in the molecular organization of AJ. VE-cadherin was mostly associated with beta-catenin and p120 in loose EC monolayers, while in long-confluent cells, these two catenins were largely replaced by plakoglobin. Inhibition of P-tyr phosphatases (PTPases) by PV markedly augmented the P-tyr content of VE-cadherin, which bound p120 and beta-catenin more efficiently, but not plakoglobin. Transfection experiments in CHO cells showed that p120 could bind to a VE-cadherin cytoplasmic region different from that responsible for beta-catenin binding, and PV stabilized this association. Overall these data indicate that endothelial AJ are dynamic structures that can be affected by the state of confluence of the cells. Tyrosine phosphorylation of VE-cadherin and its association to p120 and beta-catenin characterizes early cell contacts, while the formation of mature and cytoskeleton-connected junctions is accompanied by dephosphorylation and plakoglobin association.

Catenins in Xenopus embryogenesis and their relation to the cadherin-mediated cell-cell adhesion system

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 629-640 ◽  
Author(s):  
S. Schneider ◽  
K. Herrenknecht ◽  
S. Butz ◽  
R. Kemler ◽  
P. Hausen
Keyword(s):  
Cell Adhesion ◽  
Plasma Membranes ◽  
Early Embryo ◽  
Xenopus Embryo ◽  
Free Form ◽  
Beta Catenin ◽  
Metabolic Labelling ◽  
Adhesion System ◽  
E Cadherin ◽  
Cell Cell

In the course of an analysis of cell-cell adhesion in the Xenopus embryo, antibodies directed against alpha- and beta-catenin were applied to investigate their relation to the cadherins occurring early in this system. The results demonstrate that alpha- and beta-catenin are provided maternally and increase in amount throughout embryogenesis. Immunoprecipitations indicate that both of the catenins are complexed to U-cadherin in the early phase of embryogenesis and to E-cadherin, when it appears during gastrulation. An excess of alpha-catenin occurs in free form in the early embryo, whereas all of the beta-catenin seems to be complexed to cadherin. Synthesis of the two components throughout early embryogenesis and their binding to newly synthesized cadherins were demonstrated by metabolic labelling. The spatial distribution of alpha-catenin was analysed by immunohistology. During cleavage alpha-catenin is deposited evenly along the plasma membranes within the embryo, while the cell peripheries at the surface of the embryo remain devoid of alpha-catenin. At later stages, the pattern of alpha-catenin distribution becomes more complex. Quantitative differences in the intensity of staining along the plasma membranes in the different regions of the embryo can be distinguished. Particularly the appearance of E-cadherin in the gastrula ectoderm is accompanied by conspicuous depositions of alpha-catenin along the respective plasma membranes in this layer. All cells in the later embryo, apart from the neural crest cells, carry alpha-catenin on their plasma membranes indicating the universal character of cadherin-mediated cell-cell adhesion in the Xenopus embryo.

Differential expression of cell-cell and cell-substratum adhesion proteins along the kidney nephron

1995 ◽  
Vol 269 (6) ◽  
pp. C1433-C1449 ◽  
Author(s):  
P. A. Piepenhagen ◽  
W. J. Nelson
Keyword(s):  
Cell Adhesion ◽  
Immunofluorescence Microscopy ◽  
The Other ◽  
Beta Catenin ◽  
Desmosomal Cadherins ◽  
Functional Differences ◽  
Associated Proteins ◽  
Capillary Endothelial Cells ◽  
Mediate Cell ◽  
Cell Cell

Structural and functional differences among epithelial cells of kidney nephrons may be regulated by variations in cell-to-cell (cell-cell) and cell-to-substratum (cell-substratum) junctions. Using immunofluorescence microscopy, we demonstrate that the cadherin-associated proteins alpha- and beta-catenin are localized to basolateral membranes of cells in all nephron segments, whereas plakoglobin, a protein associated with both classical and desmosomal cadherins, is localized to noninterdigitated lateral membranes in the distal half of the nephron where it colocalizes with desmoplakin and cytokeratin K8. Plakoglobin is also present in capillary endothelial cells where staining for the other catenins and desmosomal proteins is not observed. Immunofluorescence for laminin A and alpha 6-integrin, proteins that mediate cell-substratum contacts, reveal no correlations with the other staining patterns observed. These data indicate that plakoglobin and beta-catenin subserve distinct functions in cell-cell adhesion and suggest that E-cadherin-mediated contacts generate a basal level of cell-cell adhesion, whereas desmosomal junctions provide additional strength to cell-cell contacts in the distal nephron.

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