scholarly journals A-CAM: a 135-kD receptor of intercellular adherens junctions. II. Antibody-mediated modulation of junction formation.

1986 ◽  
Vol 103 (4) ◽  
pp. 1451-1464 ◽  
Author(s):  
T Volk ◽  
B Geiger
Keyword(s):  
Cell Adhesion ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Recovery Phase ◽  
Inhibitory Effect ◽  
Cell Junctions ◽  
Specific Cell ◽  
Normal Medium ◽  
Junction Formation ◽  
Cell Cell

Intercellular adherens junctions between cultured lens epithelial cells are highly Ca2+-dependent and are readily dissociated upon chelation of extracellular Ca2+ ions. Addition of Ca2+ to EGTA-treated cells results in the recovery of cell-cell junctions including the reorganization of adherens junction-specific cell adhesion molecule (A-CAM), vinculin, and actin (Volk, T., and B. Geiger, 1986, J. Cell Biol., 103:000-000). Incubation of cells during the recovery phase with Fab' fragments of anti-A-CAM specifically inhibited the re-formation of cell-cell adherens junctions. This inhibition was accompanied by remarkable changes in microfilament organization manifested by an apparent deterioration of stress fibers and the appearance of fragmented actin bundles throughout the cytoplasm. Incubation of EGTA-dissociated cells with intact divalent anti-A-CAM antibodies in normal medium had no apparent inhibitory effect on junction formation and did not affect the assembly of actin microfilament bundles. Moreover, adherens junctions formed in the presence of the divalent antibodies became essentially Ca2+-independent, suggesting that cell-cell adhesion between them was primarily mediated by the antibodies. These studies suggest that A-CAM participates in intercellular adhesion in adherens-type junctions and point to its involvement in microfilament bundle assembly.

Plakoglobin expression and localization in zebrafish embryo development

2004 ◽  
Vol 32 (5) ◽  
pp. 797-798 ◽  
Author(s):  
E.D. Martin ◽  
M. Grealy
Keyword(s):  
Confocal Microscopy ◽  
Embryo Development ◽  
Western Blotting ◽  
Protein Level ◽  
Adherens Junctions ◽  
Cell Junctions ◽  
Specific Cell ◽  
Heart Chamber ◽  
Heart Region ◽  
Cell Cell

Plakoglobin (γ-catenin) and β-catenin are major components of the adherens junctions and can be localized to the nucleus by activation of the Wnt signalling pathway. In addition, plakoglobin is also found in desmosomes, a vertebrate-specific cell–cell adhesion structure. Plakoglobin expression and localization were examined at the protein level during zebrafish embryonic development by Western blotting and confocal microscopy. Plakoglobin was expressed throughout embryo development at the protein level. Western blotting revealed that embryonic plakoglobin protein content increased between 12- and 24-h post-fertilization (hpf). Confocal microscopy showed that at stages up to 12 hpf, plakoglobin and β-catenin were co-localized and expressed in both the nucleus and in cell–cell junctions. At 24- and 72-hpf, separate patterns were seen for plakoglobin and β-catenin. These data indicate that plakoglobin localization in the heart region shifts from adherens junctions to desmosomes during heart chamber development.

Assembly of adherens junctions is required for sphingosine 1-phosphate-induced matriptase accumulation and activation at mammary epithelial cell-cell contacts

2004 ◽  
Vol 286 (5) ◽  
pp. C1159-C1169 ◽  
Author(s):  
Ruei-Jiun Hung ◽  
Ia-Wen J. Hsu ◽  
Jennifer L. Dreiling ◽  
Mon-Juan Lee ◽  
Cicely A. Williams ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Mammary Epithelial ◽  
Cell Junctions ◽  
Cell Contacts ◽  
Cytoskeletal Rearrangement ◽  
Sphingosine 1 Phosphate ◽  
Cell Cell

Sphingosine 1-phosphate (S1P), a bioactive phospholipid, simultaneously induces actin cytoskeletal rearrangements and activation of matriptase, a membrane-associated serine protease in human mammary epithelial cells. In this study, we used a monoclonal antibody selective for activated, two-chain matriptase to examine the functional relationship between these two S1P-induced events. Ten minutes after exposure of 184 A1N4 mammary epithelial cells to S1P, matriptase was observed to accumulate at cell-cell contacts. Activated matriptase first began to appear as small spots at cell-cell contacts, and then its deposits elongated along cell-cell contacts. Concomitantly, S1P induced assembly of adherens junctions and subcortical actin belts. Matriptase localization was observed to be coincident with markers of adherens junctions at cell-cell contacts but likely not to be incorporated into the tightly bound adhesion plaque. Disruption of subcortical actin belt formation and prevention of adherens junction assembly led to prevention of accumulation and activation of the protease at cell-cell contacts. These data suggest that S1P-induced accumulation and activation of matriptase depend on the S1P-induced adherens junction assembly. Although MAb M32, directed against one of the low-density lipoprotein receptor class A domains of matriptase, blocked S1P-induced activation of the enzyme, the antibody had no effect on S1P-induced actin cytoskeletal rearrangement. Together, these data indicate that actin cytoskeletal rearrangement is necessary but not sufficient for S1P-induced activation of matriptase at cell-cell contacts. The coupling of matriptase activation to adherens junction assembly and actin cytoskeletal rearrangement may serve to ensure tight control of matriptase activity, restricted to cell-cell junctions of mammary epithelial cells.

scholarly journals A model system for cell adhesion and signal transduction in Drosophila

Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 163-176 ◽  
Author(s):  
Mark Peifer ◽  
Sandra Orsulic ◽  
Li-Mei Pai ◽  
Joseph Loureiro
Keyword(s):  
Cell Adhesion ◽  
Function Analysis ◽  
Cell Communication ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Direct Role ◽  
Junction Protein ◽  
Wingless Signaling ◽  
Segment Polarity ◽  
Cell Cell

Cells must cooperate and communicate to form a multicellular animal. Information about the molecules required for these processes have come from a variety of sources; the convergence between the studies of particular molecules by vertebrate cell biologists and the genes identified by scientists investigating development in Drosophila has been especially fruitful. We are interested in the connection between cadherin proteins that regulate cell-cell adhesion and the wingless/wnt-1 cell-cell signaling molecules controlling pattern formation during development. The Drosophila segment polarity gene armadillo, homolog of the vertebrate adherens junction protein-catenin, is required for both cell adhesion and wg signaling. We review what is known about wingless signaling in Drosophila, and discuss the role of cell-cell junctions in both cell adhesion and cell communication. We then describe the results of our preliminary structure-function analysis of Armadillo protein in both cell adhesion and wingless signaling. Finally, we discuss evidence supporting a direct role for Armadillo and adherens junction in transduction of wingless signal.

scholarly journals DLG-1 Is a MAGUK Similar to SAP97 and Is Required for Adherens Junction Formation

2001 ◽  
Vol 12 (11) ◽  
pp. 3465-3475 ◽  
Author(s):  
Bonnie L. Firestein ◽  
Christopher Rongo
Keyword(s):  
Cell Polarity ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Permeability Barrier ◽  
Cortical Actin ◽  
Interaction Domain ◽  
Amino Terminal ◽  
Junction Formation ◽  
And Function

Cellular junctions are critical for intercellular communication and for the assembly of cells into tissues. Cell junctions often consist of tight junctions, which form a permeability barrier and prevent the diffusion of lipids and proteins between cell compartments, and adherens junctions, which control the adhesion of cells and link cortical actin filaments to attachment sites on the plasma membrane. Proper tight junction formation and cell polarity require the function of membrane-associated guanylate kinases (MAGUKs) that contain the PDZ protein-protein interaction domain. In contrast, less is known about how adherens junctions are assembled. Here we describe how the PDZ-containing protein DLG-1 is required for the proper formation and function of adherens junctions in Caenorhabditis elegans. DLG-1 is a MAGUK protein that is most similar in sequence to mammalian SAP97, which is found at both synapses of the CNS, as well as at cell junctions of epithelia. DLG-1 is localized to adherens junctions, and DLG-1 localization is mediated by an amino-terminal domain shared with SAP97 but not found in other MAGUK family members. DLG-1 recruits other proteins and signaling molecules to adherens junctions, while embryos that lack DLG-1 fail to recruit the proteins AJM-1 and CPI-1 to adherens junctions. DLG-1 is required for the proper organization of the actin cytoskeleton and for the morphological elongation of embryos. In contrast to other proteins that have been observed to affect adherens junction assembly and function, DLG-1 is not required to maintain cell polarity. Our results suggest a new function for MAGUK proteins distinct from their role in cell polarity.

scholarly journals The Protein Tyrosine Phosphatase Pez Is a Major Phosphatase of Adherens Junctions and Dephosphorylates β-Catenin

2003 ◽  
Vol 14 (6) ◽  
pp. 2520-2529 ◽  
Author(s):  
Carol Wadham ◽  
Jennifer R Gamble ◽  
Mathew A Vadas ◽  
Yeesim Khew-Goodall
Keyword(s):  
Cell Adhesion ◽  
Tyrosine Phosphorylation ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Adherens Junction ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Adherens Junction Proteins ◽  
Cell Cell

Cell-cell adhesion regulates processes important in embryonal development, normal physiology, and cancer progression. It is regulated by various mechanisms including tyrosine phosphorylation. We have previously shown that the protein tyrosine phosphatase Pez is concentrated at intercellular junctions in confluent, quiescent monolayers but is nuclear in cells lacking cell-cell contacts. We show here with an epithelial cell model that Pez localizes to the adherens junctions in confluent monolayers. A truncation mutant lacking the catalytic domain acts as a dominant negative mutant to upregulate tyrosine phosphorylation at adherens junctions. We identified β-catenin, a component of adherens junctions, as a substrate of Pez by a “substrate trapping” approach and by in vitro dephosphorylation with recombinant Pez. Consistent with this, ectopic expression of the dominant negative mutant caused an increase in tyrosine phosphorylation of β-catenin, demonstrating that Pez regulates the level of tyrosine phosphorylation of adherens junction proteins, including β-catenin. Increased tyrosine phosphorylation of adherens junction proteins has been shown to decrease cell-cell adhesion, promoting cell migration as a result. Accordingly, the dominant negative Pez mutant enhanced cell motility in an in vitro “wound” assay. This suggests that Pez is also a regulator of cell motility, most likely through its action on cell-cell adhesion.

scholarly journals A Novel Role of Nectins in Inhibition of the E-Cadherin–induced Activation of Rac and Formation of Cell-Cell Adherens Junctions

2004 ◽  
Vol 15 (3) ◽  
pp. 1077-1088 ◽  
Author(s):  
Takashi Hoshino ◽  
Kazuya Shimizu ◽  
Tomoyuki Honda ◽  
Tomomi Kawakatsu ◽  
Taihei Fukuyama ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
G Protein ◽  
Adherens Junctions ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Inhibitory Effect ◽  
Small G Protein ◽  
E Cadherin ◽  
Cell Cell

Nectins are Ca2+-independent immunoglobulin (Ig)-like cell-cell adhesion molecules. The trans-interactions of nectins recruit cadherins to the nectin-based cell-cell adhesion, resulting in formation of cell-cell adherens junctions (AJs) in epithelial cells and fibroblasts. The trans-interaction of E-cadherin induces activation of Rac small G protein, whereas the trans-interactions of nectins induce activation of not only Rac but also Cdc42 small G protein. We showed by the fluorescent resonance energy transfer (FRET) imaging that the trans-interaction of E-cadherin induced dynamic activation and inactivation of Rac, which led to dynamic formation and retraction of lamellipodia. Moreover, we found here that the nectins, which did not trans-interact with other nectins (non–trans-interacting nectins), inhibited the E-cadherin–induced activation of Rac and reduced the velocity of the formation of the E-cadherin-based cell-cell AJs. The inhibitory effect of non–trans-interacting nectins was suppressed by the activation of Cdc42 induced by the trans-interactions of nectins. These results indicate a novel role of nectins in regulation of the E-cadherin–induced activation of Rac and formation of cell-cell AJs.

scholarly journals Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

2019 ◽  
Author(s):  
Azita Gorji ◽  
Pearlyn Jia Ying Toh ◽  
Yi-Chin Toh ◽  
Yusuke Toyama ◽  
Pakorn Kanchanawong
Keyword(s):  
Cell Migration ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Inhibitory Effect ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Combined Strategy ◽  
Cell Migration And Proliferation ◽  
Arterial Endothelial Cells ◽  
Cell Cell

RationaleFailure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases.ObjectivePrevious strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations.Methods and resultWe characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates.We identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization.Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation.ConclusionThe synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation.

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.

Cell-cell adhesion and signal transduction duringDictyosteliumdevelopment

2001 ◽  
Vol 114 (24) ◽  
pp. 4349-4358 ◽  
Author(s):  
Juliet C. Coates ◽  
Adrian J. Harwood
Keyword(s):  
Signal Transduction ◽  
Cell Adhesion ◽  
Structural Integrity ◽  
Adherens Junctions ◽  
Cell Signalling ◽  
Cell Junctions ◽  
Cell Contact ◽  
Multicellular Development ◽  
Mediate Cell ◽  
Cell Cell

The development of the non-metazoan eukaryote Dictyostelium discoideum displays many of the features of animal embryogenesis, including regulated cell-cell adhesion. During early development, two proteins, DdCAD-1 and csA, mediate cell-cell adhesion between amoebae as they form a loosely packed multicellular mass. The mechanism governing this process is similar to epithelial sheet sealing in animals. Although cell differentiation can occur in the absence of cell contact, regulated cell-cell adhesion is an important component of Dictyostelium morphogenesis, and a third adhesion molecule, gp150, is required for multicellular development past the aggregation stage.Cell-cell junctions that appear to be adherens junctions form during the late stages of Dictyostelium development. Although they are not essential to establish the basic multicellular body plan, these junctions are required to maintain the structural integrity of the fruiting body. The Dictyostelium β-catenin homologue Aardvark (Aar) is present in adherens junctions, which are lost in its absence. As in the case of its metazoan counterparts, Aar also has a function in cell signalling and regulates expression of the pre-spore gene psA.It is becoming clear that cell-cell adhesion is an integral part of Dictyostelium development. As in animals, cell adhesion molecules have a mechanical function and may also interact with the signal-transduction processes governing morphogenesis.

scholarly journals Golgi-associated cPLA2α Regulates Endothelial Cell–Cell Junction Integrity by Controlling the Trafficking of Transmembrane Junction Proteins

2009 ◽  
Vol 20 (19) ◽  
pp. 4225-4234 ◽  
Author(s):  
Elsa Regan-Klapisz ◽  
Vincent Krouwer ◽  
Miriam Langelaar-Makkinje ◽  
Laxman Nallan ◽  
Michael Gelb ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Intracellular Trafficking ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Cell Junction ◽  
Tight Junction Formation ◽  
Junction Formation ◽  
Junction Proteins ◽  
Cell Cell

In endothelial cells specifically, cPLA2α translocates from the cytoplasm to the Golgi complex in response to cell confluence. Considering the link between confluence and cell–cell junction formation, and the emerging role of cPLA2α in intracellular trafficking, we tested whether Golgi-associated cPLA2α is involved in the trafficking of junction proteins. Here, we show that the redistribution of cPLA2α from the cytoplasm to the Golgi correlates with adherens junction maturation and occurs before tight junction formation. Disruption of adherens junctions using a blocking anti-VE-cadherin antibody reverses the association of cPLA2α with the Golgi. Silencing of cPLA2α and inhibition of cPLA2α enzymatic activity using various inhibitors result in the diminished presence of the transmembrane junction proteins VE-cadherin, occludin, and claudin-5 at cell–cell contacts, and in their accumulation at the Golgi. Altogether, our data support the idea that VE-cadherin triggers the relocation of cPLA2α to the Golgi and that in turn, Golgi-associated cPLA2α regulates the transport of transmembrane junction proteins through or from the Golgi, thereby controlling the integrity of endothelial cell–cell junctions.

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