scholarly journals δ-catenin, an Adhesive Junction–associated Protein Which Promotes Cell Scattering

1999 ◽  
Vol 144 (3) ◽  
pp. 519-532 ◽  
Author(s):  
Qun Lu ◽  
Mercedes Paredes ◽  
Miguel Medina ◽  
Jianhua Zhou ◽  
Robert Cavallo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mdck Cells ◽  
Sequence Similarity ◽  
Ventricular Zone ◽  
Ectopic Expression ◽  
Adherens Junction ◽  
Mammalian Brain ◽  
Juxtamembrane Region ◽  
Junction Protein ◽  
Hepatocyte Growth Factor Treatment

The classical adherens junction that holds epithelial cells together consists of a protein complex in which members of the cadherin family linked to various catenins are the principal components. δ-catenin is a mammalian brain protein in the Armadillo repeat superfamily with sequence similarity to the adherens junction protein p120ctn. We found that δ-catenin can be immunoprecipitated as a complex with other components of the adherens junction, including cadherin and β-catenin, from transfected cells and brain. The interaction with cadherin involves direct contact within the highly conserved juxtamembrane region of the COOH terminus, where p120ctn also binds. In developing mouse brain, staining with δ-catenin antibodies is prominent towards the apical boundary of the neuroepithelial cells in the ventricular zone. When transfected into Madin-Darby canine kidney (MDCK) epithelial cells δ-catenin colocalized with cadherin, p120ctn, and β-catenin. The Arm domain alone was sufficient for achieving localization and coimmunoprecipitation with cadherin. The ectopic expression of δ-catenin in MDCK cells altered their morphology, induced the elaboration of lamellipodia, interfered with monolayer formation, and increased scattering in response to hepatocyte growth factor treatment. We propose that δ-catenin can regulate adhesion molecules to implement the organization of large cellular arrays necessary for tissue morphogenesis.

scholarly journals Polycystin-1 and Gα12 regulate the cleavage of E-cadherin in kidney epithelial cells

2015 ◽  
Vol 47 (2) ◽  
pp. 24-32 ◽  
Author(s):  
Jen X. Xu ◽  
Tzong-Shi Lu ◽  
Suyan Li ◽  
Yong Wu ◽  
Lai Ding ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Cell Polarity ◽  
Mdck Cells ◽  
Adherens Junction ◽  
Renal Epithelial Cells ◽  
Extracellular Milieu ◽  
Kidney Epithelial Cells ◽  
Autosomal Dominant Polycystic Kidney ◽  
E Cadherin

Interaction of polycystin-1 (PC1) and Gα12 is important for development of kidney cysts in autosomal dominant polycystic kidney disease (ADPKD). The integrity of cell polarity and cell-cell adhesions (mainly E-cadherin-mediated adherens junction) is altered in the renal epithelial cells of ADPKD. However, the key signaling pathway for this alteration is not fully understood. Madin-Darby canine kidney (MDCK) cells maintain the normal integrity of epithelial cell polarity and adherens junctions. Here, we found that deletion of Pkd1 increased activation of Gα12, which then promoted the cystogenesis of MDCK cells. The morphology of these cells was altered after the activation of Gα12. By using liquid chromatography-mass spectrometry, we found several proteins that could be related this change in the extracellular milieu. E-cadherin was one of the most abundant peptides after active Gα12 was induced. Gα12 activation or Pkd1 deletion increased the shedding of E-cadherin, which was mediated via increased ADAM10 activity. The increased shedding of E-cadherin was blocked by knockdown of ADAM10 or specific ADAM10 inhibitor GI254023X. Pkd1 deletion or Gα12 activation also changed the distribution of E-cadherin in kidney epithelial cells and caused β-catenin to shift from cell membrane to nucleus. Finally, ADAM10 inhibitor, GI254023 X, blocked the cystogenesis induced by PC1 knockdown or Gα12 activation in renal epithelial cells. Our results demonstrate that the E-cadherin/β-catenin signaling pathway is regulated by PC1 and Gα12 via ADAM10. Specific inhibition of this pathway, especially ADAM10 activity, could be a novel therapeutic regimen for ADPKD.

scholarly journals Abelson kinase regulates epithelial morphogenesis in Drosophila

2001 ◽  
Vol 155 (7) ◽  
pp. 1185-1198 ◽  
Author(s):  
Elizabeth E. Grevengoed ◽  
Joseph J. Loureiro ◽  
Traci L. Jesse ◽  
Mark Peifer
Keyword(s):  
Epithelial Cells ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Epithelial Morphogenesis ◽  
Actin Dynamics ◽  
Nonreceptor Tyrosine Kinase ◽  
Abelson Kinase ◽  
Adherens Junction Protein ◽  
Junction Protein ◽  
Guidance Receptors

Activation of the nonreceptor tyrosine kinase Abelson (Abl) contributes to the development of leukemia, but the complex roles of Abl in normal development are not fully understood. Drosophila Abl links neural axon guidance receptors to the cytoskeleton. Here we report a novel role for Drosophila Abl in epithelial cells, where it is critical for morphogenesis. Embryos completely lacking both maternal and zygotic Abl die with defects in several morphogenetic processes requiring cell shape changes and cell migration. We describe the cellular defects that underlie these problems, focusing on dorsal closure as an example. Further, we show that the Abl target Enabled (Ena), a modulator of actin dynamics, is involved with Abl in morphogenesis. We find that Ena localizes to adherens junctions of most epithelial cells, and that it genetically interacts with the adherens junction protein Armadillo (Arm) during morphogenesis. The defects of abl mutants are strongly enhanced by heterozygosity for shotgun, which encodes DE-cadherin. Finally, loss of Abl reduces Arm and α-catenin accumulation in adherens junctions, while having little or no effect on other components of the cytoskeleton or cell polarity machinery. We discuss possible models for Abl function during epithelial morphogenesis in light of these data.

Selective degradation of E-cadherin and dissolution of E-cadherin-catenin complexes in epithelial ischemia

2000 ◽  
Vol 278 (5) ◽  
pp. F847-F852 ◽  
Author(s):  
Kevin T. Bush ◽  
Tatsuo Tsukamoto ◽  
Sanjay K. Nigam
Keyword(s):  
Epithelial Cells ◽  
Mdck Cells ◽  
Transmembrane Protein ◽  
Adherens Junction ◽  
Intercellular Junctions ◽  
Atp Depletion ◽  
Cell Phenotype ◽  
Western Blots ◽  
Selective Degradation ◽  
E Cadherin

Ischemic epithelial cells are characterized by disruption of intercellular junctions and loss of apical-basolateral protein polarity, which are normally dependent on the integrity of the adherens junction (AJ). Biochemical analysis of both whole ischemic kidneys and ATP-depleted Madin-Darby canine kidney (MDCK) cells demonstrated a striking loss of E-cadherin (the transmembrane protein of the AJ) with the appearance and accumulation of an ∼80-kDa fragment reactive with anti-E-cadherin antibodies on Western blots of ATP-depleted MDCK cells. This apparent ischemia-induced degradation of E-cadherin was not blocked by either inhibitors of the major proteolytic pathways (i.e., proteasome, lysosome, or calpain), or by chelation of intracellular calcium, suggesting the involvement of a protease capable of functioning at low ATP and low calcium levels. Immunocytochemistry revealed the movement of several proteins normally comprising the AJ, including E-cadherin and β-catenin, away from lateral portions of the plasma membrane to intracellular sites. Moreover, rate-zonal centrifugation and immunoprecipitation with anti-E-cadherin and anti-β-catenin antibodies indicated that ATP depletion disrupted normal E-cadherin-catenin interactions, resulting in the dissociation of α- and γ-catenin from E-cadherin and β-catenin-containing complexes. Because the generation and maintenance of polarized epithelial cells are dependent upon E-cadherin-mediated cell-cell adhesion and normal AJ function, we propose that the rapid degradation of E-cadherin and dissolution of the AJ is a key step in the development of the ischemic epithelial cell phenotype. Furthermore, we hypothesize that the reassembly of the AJ after ischemia/ATP depletion may require a novel bioassembly mechanism involving recombination of newly synthesized and sorted E-cadherin with preexisting pools of catenins that have (temporally) redistributed intracellularly.

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 Drosophila PATJ supports adherens junction stability by modulating Myosin light chain activity

2012 ◽  
Vol 199 (4) ◽  
pp. 685-698 ◽  
Author(s):  
Arnab Sen ◽  
Zsanett Nagy-Zsvér-Vadas ◽  
Michael P. Krahn
Keyword(s):  
Epithelial Cells ◽  
Myosin Light Chain ◽  
Adherens Junction ◽  
Myosin Phosphatase ◽  
Junction Protein ◽  
Discs Large ◽  
Myosin Binding ◽  
The Stability ◽  
Key Events ◽  
Binding Subunit

The assembly and consolidation of the adherens junctions (AJs) are key events in the establishment of an intact epithelium. However, AJs are further modified to obtain flexibility for cell migration and morphogenetic movements. Intact AJs in turn are a prerequisite for the establishment and maintenance of apical–basal polarity in epithelial cells. In this study, we report that the conserved PDZ (PSD95, Discs large, ZO-1) domain–containing protein PATJ (Pals1-associated tight junction protein) was not per se crucial for the maintenance of apical–basal polarity in Drosophila melanogaster epithelial cells but rather regulated Myosin localization and phosphorylation. PATJ directly bound to the Myosin-binding subunit of Myosin phosphatase and decreased Myosin dephosphorylation, resulting in activated Myosin. Thereby, PATJ supports the stability of the Zonula Adherens. Notably, weakening of AJ in a PATJ mutant epithelium led first to a loss of Myosin from the AJ, subsequently to a disassembly of the AJ, and finally, to a loss of apical–basal polarity and disruption of the tissue.

Zbed3 Is Indispensable for Wnt Signaling Regulation of Cortical Layers Formation in Developing Brain

2021 ◽  
Author(s):  
Xiangbin Ruan ◽  
Gaoao Liu ◽  
Jiafeng Zhou ◽  
Pan Chen ◽  
Changjie Sun ◽  
...  
Keyword(s):  
Radial Glia ◽  
Ventricular Zone ◽  
Ectopic Expression ◽  
Neural Progenitors ◽  
Developing Brain ◽  
Mammalian Brain ◽  
Dependent Manner ◽  
Layer Formation ◽  
Proliferation And Differentiation ◽  
Neuronal Layer

Abstract Wnt/β-catenin signaling plays multiple important roles during mammalian brain development, and it regulates the proliferation and differentiation of neural progenitors in a context-dependent manner and affects neocortex layer formation. However, the specific role of Wnt/β-catenin in neuronal layer fate determination in the neocortex is still unclear. Here, we report that Zbed3, which is a positive regulator of Wnt/β-catenin signaling, colocalizes with β-catenin at the endfeet of radial glia in the ventricular zone of embryo mouse neocortex. Overexpression and knockdown of Zbed3 increased and decreased the activity of Wnt/β-catenin signaling in the neocortex, respectively. Interestingly, knockdown of Zbed3 in vivo could significantly shift neuronal fates from deep layers to upper layers but is not required for the proliferation and differentiation of neural progenitors. Overexpression of Zbed3 led to increased generation of deep-layer neurons without impairing cell cycle exit of neural progenitors. More importantly, knockdown of Zbed3 could effectively block the effects of the ectopic expression of stabilized β-catenin on neocortex layer formation. Hence, our results demonstrate that Zbed3 is indispensable for Wnt/β-catenin signaling regulating neuronal layer fates in the developing brain.

scholarly journals Differential regulation of junctional complex assembly in renal epithelial cell lines

2003 ◽  
Vol 285 (1) ◽  
pp. C102-C111 ◽  
Author(s):  
Shobha Gopalakrishnan ◽  
Mark A. Hallett ◽  
Simon J. Atkinson ◽  
James. A. Marrs
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Rho Gtpase ◽  
Mdck Cells ◽  
Adherens Junction ◽  
Stress Fiber ◽  
Cell Junctions ◽  
Junctional Complex ◽  
Complex Assembly ◽  
E Cadherin

Several signaling pathways that regulate tight junction and adherens junction assembly are being characterized. Calpeptin activates stress fiber assembly in fibroblasts by inhibiting SH2-containing phosphatase-2 (SHP-2), thereby activating Rho-GTPase signaling. Here, we have examined the effects of calpeptin on stress fiber and junctional complex assembly in Madin-Darby canine kidney (MDCK) and LLC-PK epithelial cells. Calpeptin induced disassembly of stress fibers and inhibition of Rho GTPase activity in MDCK cells. Interestingly, calpeptin augmented stress fiber formation in LLC-PK epithelial cells. Calpeptin treatment of MDCK cells resulted in a displacement of zonula occludens-1 (ZO-1) and occludin from cell-cell junctions and a loss of phosphotyrosine on ZO-1 and ZO-2, without any detectable effect on tight junction permeability. Surprisingly, calpeptin increased paracellular permeability in LLC-PK cells even though it did not affect tight junction assembly. Calpeptin also modulated adherens junction assembly in MDCK cells but not in LLC-PK cells. Calpeptin treatment of MDCK cells induced redistribution of E-cadherin and β-catenin from intercellular junctions and reduced the association of p120ctn with the E-cadherin/catenin complex. Together, our studies demonstrate that calpeptin differentially regulates stress fiber and junctional complex assembly in MDCK and LLC-PK epithelial cells, indicating that these pathways may be regulated in a cell line-specific manner.

scholarly journals Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis.

1996 ◽  
Vol 134 (1) ◽  
pp. 133-148 ◽  
Author(s):  
R T Cox ◽  
C Kirkpatrick ◽  
M Peifer
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cells ◽  
Embryonic Development ◽  
Cell Polarity ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Morphogenetic Movements ◽  
Junction Protein ◽  
Normal Embryonic Development ◽  
Cell Cell

Morphological and biochemical analyses have identified a set of proteins which together form a structure known as the adherens junction. Elegant experiments in tissue culture support the idea that adherens junctions play a key role in cell-cell adhesion and in organizing cells into epithelia. During normal embryonic development, cells quickly organize epithelia; these epithelial cells participate in many of the key morphogenetic movements of gastrulation. This prompted the hypothesis that adherens junctions ought to be critical for normal embryonic development. Drosophila Armadillo, the homologue of vertebrate beta-catenin, is a core component of the adherens junction protein complex and has been hypothesized to be essential for adherens junction function in vivo. We have used an intermediate mutant allele of armadillo, armadilloXP33, to test these hypotheses in Drosophila embryos. Adherens junctions cannot assemble in the absence of Armadillo, leading to dramatic defects in cell-cell adhesion. The epithelial cells of the embryo lose adhesion to each other, round up, and apparently become mesenchymal. Mutant cells also lose their normal cell polarity. These disruptions in the integrity of epithelia block the appropriate morphogenetic movements of gastrulation. These results provide the first demonstration of the effect of loss of adherens junctions on Drosophila embryonic development.

scholarly journals p120 Modulates LPS-Induced NF-κB Activation Partially through RhoA in Bronchial Epithelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Lingzhi Qin ◽  
Shenghui Qin ◽  
Yanli Zhang ◽  
Chao Zhang ◽  
Heng Ma ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Adherens Junction ◽  
Bronchial Epithelial Cells ◽  
Rock Inhibitor ◽  
Bronchial Epithelial ◽  
Rhoa Activity ◽  
Junction Protein

p120-Catenin (p120) is an adherens junction protein recognized to regulate cell-cell adhesion. Emerging evidence indicates that p120 may also play an important role in inflammatory responses, and the regulatory mechanisms are still unknown. In the present study, we showed that p120 was associated with airway inflammation. p120 downregulation induced nuclear factor-κB (NF-κB) activation, accompanied with IκBαdegradation, p65 nuclear translocation, and increased expression of interleukin-8 (IL-8) in lipopolysaccharide (LPS)- treated C57BL mice and human bronchial epithelial cells (BECs). Moreover, we first found that p120 directly coprecipitated with RhoA in BECs. After LPS stimulation, although total RhoA and p120-bound RhoA were unchanged, RhoA activity was increased. Y27632, a ROCK inhibitor, could partially inhibit nuclear translocation of p65. Overexpression of p120 inactivated RhoA and NF-κB in BECs, whereas p120 loss significantly increased RhoA activity, p65 nuclear translocation, and IL-8 expression. Taken together, our study supports the regulatory role of p120 in airway inflammation and reveals that p120 may modulate NF-κB signaling partially through RhoA.

Active Rab11 and functional recycling endosome are required for E-cadherin trafficking and lumen formation during epithelial morphogenesis

2008 ◽  
Vol 295 (2) ◽  
pp. C545-C556 ◽  
Author(s):  
Marion Desclozeaux ◽  
Juliana Venturato ◽  
Fiona G. Wylie ◽  
Jason G. Kay ◽  
Shannon R. Joseph ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Mdck Cells ◽  
Adherens Junction ◽  
Dominant Negative ◽  
Epithelial Morphogenesis ◽  
Live Cells ◽  
Recycling Endosome ◽  
Lumen Formation ◽  
Junction Protein ◽  
E Cadherin

The correct targeting and trafficking of the adherens junction protein epithelial cadherin (E-cadherin) is a major determinant for the acquisition of epithelial cell polarity and for the maintenance of epithelial integrity. The compartments and trafficking components required to sort and transport E-cadherin to the basolateral cell surface remain to be fully defined. On the basis of previous data, we know that E-cadherin is trafficked via the recycling endosome (RE) in nonpolarized and newly polarized cells. Here we explore the role of the RE throughout epithelial morphogenesis in MDCK monolayers and cysts. Time-lapse microscopy in live cells, altering RE function biochemically, and expressing a dominant-negative form of Rab11 (DN-Rab11), each showed that the RE is always requisite for E-cadherin sorting and trafficking. The RE remained important for E-cadherin trafficking in MDCK cells from a nonpolarized state through to fully formed, polarized epithelial monolayers. During the development of epithelial cysts, DN-Rab11 disrupted E-cadherin targeting and trafficking, the subapical localization of pERM and actin, and cyst lumen formation. This final effect demonstrated an early and critical interdependence of Rab11 and the RE for E-cadherin targeting, apical membrane formation, and cell polarity in cysts.

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