scholarly journals A core function for p120-catenin in cadherin turnover

2003 ◽  
Vol 163 (3) ◽  
pp. 525-534 ◽  
Author(s):  
Michael A. Davis ◽  
Renee C. Ireton ◽  
Albert B. Reynolds
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Complete Loss ◽  
Vascular Endothelial ◽  
P120 Catenin ◽  
Epithelial Cadherin ◽  
Sirna Expression ◽  
Core Function ◽  
Dose Dependent ◽  
E Cadherin

p120-catenin stabilizes epithelial cadherin (E-cadherin) in SW48 cells, but the mechanism has not been established. Here, we show that p120 acts at the cell surface to control cadherin turnover, thereby regulating cadherin levels. p120 knockdown by siRNA expression resulted in dose-dependent elimination of epithelial, placental, neuronal, and vascular endothelial cadherins, and complete loss of cell–cell adhesion. ARVCF and δ-catenin were functionally redundant, suggesting that proper cadherin-dependent adhesion requires the presence of at least one p120 family member. The data reveal a core function of p120 in cadherin complexes, and strongly predict a dose-dependent loss of E-cadherin in tumors that partially or completely down-regulate p120.

scholarly journals Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

2021 ◽  
Vol 15 (1) ◽  
pp. 1-17
Author(s):  
Sarah Alsharif ◽  
Pooja Sharma ◽  
Karina Bursch ◽  
Rachel Milliken ◽  
Van Lam ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Mcf7 Cells ◽  
Keratin 19 ◽  
E Cadherin ◽  
Cell Cell

A functional test for maternally inherited cadherin in Xenopus shows its importance in cell adhesion at the blastula stage

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 49-57 ◽  
Author(s):  
J. Heasman ◽  
D. Ginsberg ◽  
B. Geiger ◽  
K. Goldstone ◽  
T. Pratt ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Protein Level ◽  
Mrna Level ◽  
Functional Test ◽  
Gastrula Stage ◽  
Blastula Stage ◽  
Xenopus Development ◽  
Dose Dependent ◽  
Embryonic Ectoderm ◽  
E Cadherin

We report here on the consequences of reducing the expression of EP-cadherin at the earliest stages of Xenopus development. Injection of oligodeoxynucleotides antisense to maternal EP-cadherin mRNA into full-grown oocytes reduced the mRNA level in oocytes, and the protein level in blastulae. Adhesion between blastomeres was significantly reduced, as seen in whole embryos, and in assays of the ability of blastomeres to reaggregate in culture. This effect was especially conspicuous in the inner cells of the blastula and included the disruption of the blastocoel. The severity of the EP-cadherin mRNA depletion and of the disaggregation phenotype was dose dependent. This phenotype was rescued by the injection into EP-cadherin mRNA-depleted oocytes of the mRNA coding for a related cadherin, E-cadherin, that is normally expressed at the gastrula stage in the embryonic ectoderm.

scholarly journals A molecular mechanism directly linking E-cadherin adhesion to initiation of epithelial cell surface polarity

2007 ◽  
Vol 178 (2) ◽  
pp. 323-335 ◽  
Author(s):  
Lene N. Nejsum ◽  
W. James Nelson
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Cell Surface ◽  
Basolateral Membrane ◽  
Surface Polarity ◽  
Cell Contacts ◽  
Protein Receptors ◽  
Epithelial Cell Surface ◽  
E Cadherin ◽  
Cell Cell

Mechanisms involved in maintaining plasma membrane domains in fully polarized epithelial cells are known, but when and how directed protein sorting and trafficking occur to initiate cell surface polarity are not. We tested whether establishment of the basolateral membrane domain and E-cadherin–mediated epithelial cell–cell adhesion are mechanistically linked. We show that the basolateral membrane aquaporin (AQP)-3, but not the equivalent apical membrane AQP5, is delivered in post-Golgi structures directly to forming cell–cell contacts where it co-accumulates precisely with E-cadherin. Functional disruption of individual components of a putative lateral targeting patch (e.g., microtubules, the exocyst, and soluble N-ethylmaleimide–sensitive factor attachment protein receptors) did not inhibit cell–cell adhesion or colocalization of the other components with E-cadherin, but each blocked AQP3 delivery to forming cell–cell contacts. Thus, components of the lateral targeting patch localize independently of each other to cell–cell contacts but collectively function as a holocomplex to specify basolateral vesicle delivery to nascent cell–cell contacts and immediately initiate cell surface polarity.

scholarly journals Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion

2012 ◽  
Vol 23 (11) ◽  
pp. 2092-2108 ◽  
Author(s):  
Yuliya I. Petrova ◽  
MarthaJoy M. Spano ◽  
Barry M. Gumbiner
Keyword(s):  
Cell Surface ◽  
Conformational Changes ◽  
Binding Sites ◽  
Calcium Binding ◽  
Cell Types ◽  
P120 Catenin ◽  
Physiological Regulation ◽  
Conformational Epitopes ◽  
Calcium Binding Sites ◽  
E Cadherin

We investigated changes in cadherin structure at the cell surface that regulate its adhesive activity. Colo 205 cells are nonadhesive cells with a full but inactive complement of E-cadherin–catenin complexes at the cell surface, but they can be triggered to adhere and form monolayers. We were able to distinguish the inactive and active states of E-cadherin at the cell surface by using a special set of monoclonal antibodies (mAbs). Another set of mAbs binds E-cadherin and strongly activates adhesion. In other epithelial cell types these activating mAbs inhibit growth factor–induced down-regulation of adhesion and epithelial morphogenesis, indicating that these phenomena are also controlled by E-cadherin activity at the cell surface. Both types of mAbs recognize conformational epitopes at different interfaces between extracellular cadherin repeat domains (ECs), especially near calcium-binding sites. Activation also induces p120-catenin dephosphorylation, as well as changes in the cadherin cytoplasmic domain. Moreover, phospho-site mutations indicate that dephosphorylation of specific Ser/Thr residues in the N-terminal domain of p120-catenin mediate adhesion activation. Thus physiological regulation of the adhesive state of E-cadherin involves physical and/or conformational changes in the EC interface regions of the ectodomain at the cell surface that are mediated by catenin-associated changes across the membrane.

The homeodomain transcription factors Cdx1 and Cdx2 induce E-cadherin adhesion activity by reducing β- and p120-catenin tyrosine phosphorylation

2007 ◽  
Vol 293 (1) ◽  
pp. G54-G65 ◽  
Author(s):  
Toshihiko Ezaki ◽  
Rong-Jun Guo ◽  
Hong Li ◽  
Albert B. Reynolds ◽  
John P. Lynch
Keyword(s):  
Transcription Factors ◽  
Cell Adhesion ◽  
Tyrosine Phosphorylation ◽  
Intestinal Cell ◽  
Specific Gene ◽  
P120 Catenin ◽  
Cdx2 Expression ◽  
E Cadherin ◽  
Cell Cell ◽  
Homeodomain Transcription Factors

The homeodomain transcription factors Cdx1 and Cdx2 are regulators of intestine-specific gene expression. They also regulate intestinal cell differentiation and proliferation; however, these effects are poorly understood. Previously, we have shown that expression of Cdx1 or Cdx2 in human Colo 205 cells induces a mature colonocyte morphology characterized by the induction of a polarized, columnar shape with apical microvilli and strong cell-cell adhesion. To elucidate the mechanism underlying this phenomenon, we investigated the adherens junction complex. Cdx1 or Cdx2 expression reduced Colo 205 cell migration and invasion in vitro, suggesting a physiologically significant change in cadherin function. However, Cdx expression did not significantly effect E-cadherin, α-, β-, or γ-catenin, or p120-catenin protein levels. Additionally, no alteration in their intracellular distribution was observed. Cdx expression did not alter the coprecipitation of β-catenin with E-cadherin; however, it did reduce p120-catenin-E-cadherin coprecipitation. Tyrosine phosphorylation of β- and p120-catenin is known to disrupt E-cadherin-mediated cell adhesion and is associated with robust p120-catenin/E-cadherin interactions. We specifically investigated β- and p120-catenin for tyrosine phosphorylation and found that it was significantly diminished by Cdx1 or Cdx2 expression. We restored β- and p120-catenin tyrosine phosphorylation in Cdx2-expressing cells by knocking down the expression of protein tyrosine phosphatase 1B and noted a significant decline in cell-cell adhesion. We conclude that Cdx expression in Colo 205 cells induces E-cadherin-dependent cell-cell adhesion by reducing β- and p120-catenin tyrosine phosphorylation. Ascertaining the mechanism for this novel Cdx effect may improve our understanding of the regulation of cell-cell adhesion in the colonic epithelium.

scholarly journals Levels of Soluble E-Cadherin in Breast, Gastric, and Colorectal Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ombretta Repetto ◽  
Paolo De Paoli ◽  
Valli De Re ◽  
Vincenzo Canzonieri ◽  
Renato Cannizzaro
Keyword(s):  
Cell Adhesion ◽  
Cancer Cells ◽  
Body Fluids ◽  
Colorectal Cancers ◽  
Protein Fragment ◽  
Epithelial Cadherin ◽  
Cancer Dynamics ◽  
E Cadherin

Soluble E-cadherin is a 80 kDa protein fragment coming from the proteolytic cleavage of the extracellular domain of the full length epithelial cadherin, a molecule involved in cell adhesion/polarity and tissue morphogenesis. In comparison with normal epithelia, cancer cells show a decreased cadherin-mediated intercellular adhesion, and sE-cad levels normally increase in body fluids (blood and urine). This review focuses on soluble E-cadherin in sera of patients affected by three solid cancers (breast, gastric, and colorectal cancers) and how its levels correlate or not with some cancer parameters (e.g., dimension, progression, and localisation). We will describe the main proteomics approaches adopted to measure sE-cad bothin vivoandin vitroand the most important findings about its behaviour in cancer dynamics.

scholarly journals Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin.

1992 ◽  
Vol 118 (3) ◽  
pp. 671-679 ◽  
Author(s):  
K A Knudsen ◽  
M J Wheelock
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Molecular Mass ◽  
Beta Catenin ◽  
Calcium Dependent ◽  
Intracellular Proteins ◽  
Dependent Cell ◽  
Cell Surface Glycoproteins ◽  
E Cadherin ◽  
Cell Cell

E- and N-cadherin are members of a family of calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, the transmembrane cadherins self-associate, while, intracellularly, they interact with the actin-based cytoskeleton. Several intracellular proteins, collectively termed catenins, have been noted to co-immunoprecipitate with E- and N-cadherin and are thought to be involved in linking the cadherins to the cytoskeleton. Two catenins have been identified recently: a 102-kD vinculin-like protein (alpha-catenin) and a 92-kD Drosophila armadillo/plakoglobin-like protein (beta-catenin). Here, we show that plakoglobin, or an 83-kD plakoglobin-like protein, co-immunoprecipitates and colocalizes with both E- and N-cadherin. The 83-kD protein is immunologically distinct from the 92-kD beta-catenin and, because of its molecular mass, likely represents the cadherin-associated protein called gamma-catenin. Thus, two different members of a plakoglobin family associate with N- and E-cadherin and, together with the 102-kD alpha-catenin, appear to participate in linking the cadherins to the actin-based cytoskeleton.

Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1

2001 ◽  
Vol 114 (1) ◽  
pp. 111-118 ◽  
Author(s):  
V. Noe ◽  
B. Fingleton ◽  
K. Jacobs ◽  
H.C. Crawford ◽  
S. Vermeulen ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Collagen Type ◽  
Cell Aggregation ◽  
Collagen Type I ◽  
Type I ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Dependent Cell ◽  
Mcf 7 ◽  
E Cadherin

The function of many transmembrane molecules can be altered by cleavage and subsequent release of their ectodomains. We have investigated ectodomain cleavage of the cell-cell adhesion and signal-transducing molecule E-cadherin. The E-cadherin ectodomain is constitutively shed from the surface of MCF-7 and MDCKts.srcC12 cells in culture. Release of the 80 kDa soluble E-cadherin fragment is stimulated by phorbol-12-myristate-13-acetate and is inhibited by overexpression of the tissue inhibitor of metalloproteinases-2. The metalloproteinases matrilysin and stromelysin-1 both cleave E-cadherin at the cell surface and release sE-CAD into the medium. The soluble E-cadherin fragment thus released inhibits E-cadherin functions in a paracrine way, as indicated by induction of invasion into collagen type I and inhibition of E-cadherin-dependent cell aggregation. Our results, therefore, suggest a novel mechanism by which metalloproteinases can influence invasion.

scholarly journals E-cadherin endocytosis is modulated by p120-catenin through the opposing actions of RhoA and Arf1

2018 ◽  
Author(s):  
Joshua Greig ◽  
Natalia A. Bulgakova
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Actin Dynamics ◽  
P120 Catenin ◽  
Vital Importance ◽  
C Terminus ◽  
Opposing Effects ◽  
Actin Remodelling ◽  
Tissue Tension ◽  
E Cadherin

AbstractThe regulation of E-cadherin at the plasma membrane by endocytosis is of vital importance for developmental and disease. p120-catenin, which binds to the E-cadherin C-terminus, can both promote and inhibit E-cadherin endocytosis. However, little is known about what determines the directionality of p120-catenin activity, and the molecules downstream. Here, we have discovered that p120-catenin fine-tunes the clathrin-mediated endocytosis of E-cadherin in Drosophila embryonic epidermal cells. It simultaneously activated two actin-remodelling pathways with opposing effects: RhoA, which stabilized E-cadherin at the membrane, and Arf1, which promoted internalization. Epistasis experiments revealed that RhoA additionally inhibited Arf1. E-cadherin was efficiently endocytosed only in the presence of intermediate p120-catenin amounts with too little and too much p120-catenin inhibiting E-cadherin endocytosis. Finally, we found that p120-catenin levels altered the tension of the plasma membrane. Altogether, this shows that p120-catenin is a central hub which co-ordinates cell adhesion, endocytosis, and actin dynamics with tissue tension.

scholarly journals Downregulation of Rap1GAP in Human Tumor Cells Alters Cell/Matrix and Cell/Cell Adhesion

2010 ◽  
Vol 30 (13) ◽  
pp. 3262-3274 ◽  
Author(s):  
Oxana M. Tsygankova ◽  
Changqing Ma ◽  
Waixing Tang ◽  
Christopher Korch ◽  
Michael D. Feldman ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Tumor Cells ◽  
Adherens Junction ◽  
Protein Distribution ◽  
P120 Catenin ◽  
Cell Contacts ◽  
Cell Matrix ◽  
Junction Protein ◽  
E Cadherin ◽  
Cell Cell

ABSTRACT Rap1GAP expression is decreased in human tumors. The significance of its downregulation is unknown. We show that Rap1GAP expression is decreased in primary colorectal carcinomas. To elucidate the advantages conferred on tumor cells by loss of Rap1GAP, Rap1GAP expression was silenced in human colon carcinoma cells. Suppressing Rap1GAP induced profound alterations in cell adhesion. Rap1GAP-depleted cells exhibited defects in cell/cell adhesion that included an aberrant distribution of adherens junction proteins. Depletion of Rap1GAP enhanced adhesion and spreading on collagen. Silencing of Rap expression normalized spreading and restored E-cadherin, β-catenin, and p120-catenin to cell/cell contacts, indicating that unrestrained Rap activity underlies the alterations in cell adhesion. The defects in adherens junction protein distribution required integrin signaling as E-cadherin and p120-catenin were restored at cell/cell contacts when cells were plated on poly-l-lysine. Unexpectedly, Src activity was increased in Rap1GAP-depleted cells. Inhibition of Src impaired spreading and restored E-cadherin at cell/cell contacts. These findings provide the first evidence that Rap1GAP contributes to cell/cell adhesion and highlight a role for Rap1GAP in regulating cell/matrix and cell/cell adhesion. The frequent downregulation of Rap1GAP in epithelial tumors where alterations in cell/cell and cell/matrix adhesion are early steps in tumor dissemination supports a role for Rap1GAP depletion in tumor progression.

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