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 N-Cadherin Association with Lipid Rafts Regulates Its Dynamic Assembly at Cell-Cell Junctions in C2C12 Myoblasts

2005 ◽  
Vol 16 (5) ◽  
pp. 2168-2180 ◽  
Author(s):  
Marie Causeret ◽  
Nicolas Taulet ◽  
Franck Comunale ◽  
Cyril Favard ◽  
Cécile Gauthier-Rouvière
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Cell Junctions ◽  
Cell Contact ◽  
C2c12 Myoblasts ◽  
Cell Contacts ◽  
Dynamic Assembly ◽  
Cell Cell

Cadherins are homophilic cell-cell adhesion molecules implicated in cell growth, differentiation, and organization into tissues during embryonic development. They accumulate at cell-cell contact sites and act as adhesion-activated signaling receptors. Here, we show that the dynamic assembly of N-cadherin at cell-cell contacts involves lipid rafts. In C2C12 myoblasts, immunofluorescence and biochemical experiments demonstrate that N-cadherin present at cell-cell contacts is colocalized with lipid rafts. Disruption of lipid rafts leads to the inhibition of cell-cell adhesion and disorganization of N-cadherin–dependent cell-cell contacts without modifying the association of N-cadherin with catenins and its availability at the plasma membrane. Fluorescent recovery after photobleaching experiments demonstrate that at the dorsal plasma membrane, lipid rafts are not directly involved in the diffusional mobility of N-cadherin. In contrast, at cell-cell junctions N-cadherin association with lipid rafts allows its stabilization enabling the formation of a functional adhesive complex. We show that lipid rafts, as homophilic interaction and F-actin association, stabilize cadherin-dependent adhesive complexes. Homophilic interactions and F-actin association of N-cadherin are both required for its association to lipid rafts. We thus identify lipid rafts as new regulators of cadherin-mediated cell adhesion.

scholarly journals Septin Roles and Mechanisms in Organization of Endothelial Cell Junctions

2020 ◽  
Author(s):  
Joanna Kim ◽  
John A. Cooper
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adherens Junctions ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cell Contact ◽  
Junction Molecules ◽  
Tnf Α ◽  
Multiple Cell ◽  
Cell Cell

AbstractSeptins play an important role in regulating the barrier function of the endothelial monolayer of the microvasculature. Depletion of septin 2 protein alters the organization of vascular endothelial (VE)-cadherin at cell-cell adherens junctions as well as the dynamics of membrane protrusions at endothelial cell-cell contact sites. Here, we report the discovery that localization of septin 2 at endothelial cell junctions is important for the distribution of a number of other junctional molecules. We also found that treatment of microvascular endothelial cells with the inflammatory mediator TNF-α led to sequestration of septin 2 away from cell junctions and into the cytoplasm, without an effect on the overall level of septin 2 protein. Interestingly, TNF-α treatment of endothelial monolayers produced effects similar to those of depletion of septin 2 on various molecular components of adherens junctions (AJs) and tight junctions (TJs). Immunofluorescence staining revealed disruption of the integrity of AJs and TJs at cell-cell junctions without significant changes in protein expression except for VE-cadherin and nectin-2. To investigate the mechanism of junctional localization of septin 2, we mutated the polybasic motif of septin 2, which is proposed to interact with PIP2 in the plasma membrane. Overexpression of PIP2-binding mutant (PIP2BM) septin 2 led to loss of septin 2 from cell junctions with accumulation in the cytoplasm. This redistribution of septin 2 away from the membrane led to effects on cell junction molecules similar to those observed for depletion of septin 2. We conclude that septin localization to the membrane is essential for function and that septins support the localization of multiple cell junction molecules in endothelial cells.

scholarly journals Different effects of dominant negative mutants of desmocollin and desmoglein on the cell-cell adhesion of keratinocytes

2000 ◽  
Vol 113 (10) ◽  
pp. 1803-1811
Author(s):  
Y. Hanakawa ◽  
M. Amagai ◽  
Y. Shirakata ◽  
K. Sayama ◽  
K. Hashimoto
Keyword(s):  
Cell Adhesion ◽  
Adherens Junctions ◽  
Dominant Negative ◽  
Cell Contact ◽  
Beta Catenin ◽  
Hacat Cells ◽  
Subsequent Formation ◽  
Contact Sites ◽  
E Cadherin ◽  
Cell Cell

Desmosomes contain two types of cadherin: desmocollin (Dsc) and desmoglein (Dsg). In this study, we examined the different roles that Dsc and Dsg play in the formation of desmosomes, by using dominant-negative mutants. We constructed recombinant adenoviruses (Ad) containing truncated mutants of E-cadherin, desmocollin 3a, and desmoglein 3 lacking a large part of their extracellular domains (EcaddeltaEC, Dsc3adeltaEC, Dsg3deltaEC), using the Cre-loxP Ad system to circumvent the problem of the toxicity of the mutants to virus-producing cells. When Dsc3adeltaEC Ad-infected HaCaT cells were cultured with high levels of calcium, E-cadherin and beta-catenin, which are marker molecules for the adherens junction, disappeared from the cell-cell contact sites, and cell-cell adhesion was disrupted. This also occurred in the cells infected with EcaddeltaEC Ad. With Dsg3deltaEC Ad infection, keratin insertion at the cell-cell contact sites was inhibited and desmoplakin, a marker of desmosomes, was stained in perinuclear dots while the adherens junctions remained intact. Dsc3adeltaEC Ad inhibited the induction of adherens junctions and the subsequent formation of desmosomes with the calcium shift, while Dsg3deltaEC Ad only inhibited the formation of desmosomes. To further determine whether Dsc3adeltaEC directly affected adherens junctions, mouse fibroblast L cells transfected with E-cadherin (LEC5) were infected with these mutant Ads. Both Dsc3adeltaEC and EcaddeltaEC inhibited the cell-cell adhesion of LEC5 cells, as determined by the cell aggregation assay, while Dsg3deltaEC did not. These results indicate that the dominant negative effects of Dsg3deltaEC were restricted to desmosomes, while those of Dsc3adeltaEC were observed in both desmosomes and adherens junctions. Furthermore, the cytoplasmic domain of Dsc3adeltaEC coprecipitated both plakoglobin and beta-catenin in HaCaT cells. In addition, beta-catenin was found to bind the endogenous Dsc in HaCaT cells. These findings lead us to speculate that Dsc interacts with components of the adherens junctions through beta-catenin, and plays a role in nucleating desmosomes after the adherens junctions have been established.

scholarly journals Disruption of epithelial cell-cell adhesion by exogenous expression of a mutated nonfunctional N-cadherin.

1993 ◽  
Vol 4 (1) ◽  
pp. 37-47 ◽  
Author(s):  
T Fujimori ◽  
M Takeichi
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Extracellular Domain ◽  
Normal Function ◽  
Cell Junctions ◽  
Cell Contact ◽  
Intracellular Domain ◽  
C Terminus ◽  
Exogenous Expression ◽  
Cell Cell

Cadherins, a family of transmembrane cell-cell adhesion receptors, require interactions with the cytoskeleton for normal function. To assess the mechanisms of these interactions, we studied the effect of exogenous expression of a mutant N-cadherin, cN390 delta; on epithelial cell-cell adhesion. The intracellular domain of cN390 delta was intact but its extracellular domain was largely deleted so that this molecule was not functional for cell adhesion. cDNA of cN390 delta was attached to the metallothionein promoter, and introduced into the keratinocyte line PAM212 expressing endogenous E- and P-cadherin. When the expression of cN390 delta was induced by Zn2+, cadherin-dependent adhesion of the transfected cells was inhibited, resulting in the dispersion of cell colonies, although their contacts were maintained under high cell density conditions. In these cultures, cN390 delta was expressed not only on the free surfaces of the cells but also at cell-cell junctions. The endogenous cadherins were concentrated at cell-cell junctions under normal conditions. As a result of cN390 delta expression, however, the endogenous cadherins localizing at the cell-cell junctions were largely diminished, suggesting that these molecules were replaced by the mutant molecules at these sites. As a control, we transfected the same cell line with cDNA of a truncated form of N-cadherin cadherin whose intracellular C terminus had been deleted leaving the extracellular domain intact. This molecule had no effect on cell-cell adhesion, nor did it localize to cell-cell contact sites. We also found that the association of the endogenous cadherins with alpha- and beta-catenins and plakoglobin was not affected by the expression of cN390 delta, which also formed a complex with these molecules, suggesting that no competition occurred between the endogenous and exogenous cadherins for these cytoplasmic proteins. These and other additional results suggest that the nonfunctional cadherins whose intracellular domain is intact occupy the sites where the endogenous cadherins should localize, through interactions with the cytoskeleton, and inhibit the cadherin adhesion system.

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.

scholarly journals The Ras Target AF-6 Interacts with ZO-1 and Serves as a Peripheral Component of Tight Junctions in Epithelial Cells

1997 ◽  
Vol 139 (3) ◽  
pp. 785-795 ◽  
Author(s):  
Takaharu Yamamoto ◽  
Naozumi Harada ◽  
Kyoko Kano ◽  
Shin-ichiro Taya ◽  
Eli Canaani ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Adherens Junctions ◽  
Pdz Domain ◽  
Cell Junctions ◽  
Cell Contact ◽  
Fusion Partner ◽  
Cell Contacts ◽  
Contact Sites ◽  
Cell Cell

The dynamic rearrangement of cell–cell junctions such as tight junctions and adherens junctions is a critical step in various cellular processes, including establishment of epithelial cell polarity and developmental patterning. Tight junctions are mediated by molecules such as occludin and its associated ZO-1 and ZO-2, and adherens junctions are mediated by adhesion molecules such as cadherin and its associated catenins. The transformation of epithelial cells by activated Ras results in the perturbation of cell–cell contacts. We previously identified the ALL-1 fusion partner from chromosome 6 (AF-6) as a Ras target. AF-6 has the PDZ domain, which is thought to localize AF-6 at the specialized sites of plasma membranes such as cell–cell contact sites. We investigated roles of Ras and AF-6 in the regulation of cell–cell contacts and found that AF-6 accumulated at the cell–cell contact sites of polarized MDCKII epithelial cells and had a distribution similar to that of ZO-1 but somewhat different from those of catenins. Immunoelectron microscopy revealed a close association between AF-6 and ZO-1 at the tight junctions of MDCKII cells. Native and recombinant AF-6 interacted with ZO-1 in vitro. ZO-1 interacted with the Ras-binding domain of AF-6, and this interaction was inhibited by activated Ras. AF-6 accumulated with ZO-1 at the cell–cell contact sites in cells lacking tight junctions such as Rat1 fibroblasts and PC12 rat pheochromocytoma cells. The overexpression of activated Ras in Rat1 cells resulted in the perturbation of cell–cell contacts, followed by a decrease of the accumulation of AF-6 and ZO-1 at the cell surface. These results indicate that AF-6 serves as one of the peripheral components of tight junctions in epithelial cells and cell–cell adhesions in nonepithelial cells, and that AF-6 may participate in the regulation of cell–cell contacts, including tight junctions, via direct interaction with ZO-1 downstream of Ras.

Microtubule dynamics and Rac-1 signaling independently regulate barrier function in lung epithelial cells

2007 ◽  
Vol 293 (5) ◽  
pp. L1321-L1331 ◽  
Author(s):  
Magdalena J. Lorenowicz ◽  
Mar Fernandez-Borja ◽  
Anne-Marieke D. van Stalborch ◽  
Marian A. J. A. van Sterkenburg ◽  
Pieter S. Hiemstra ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Lung Epithelial Cells ◽  
Cell Junctions ◽  
Epithelial Barrier ◽  
Cell Contact ◽  
Epithelial Barrier Function ◽  
Lung Epithelial ◽  
Cell Cell

Cadherin-mediated cell-cell adhesion controls the morphology and function of epithelial cells and is a critical component of the pathology of chronic inflammatory disorders. Dynamic interactions between cadherins and the actin cytoskeleton are required for stable cell-cell contact. Besides actin, microtubules also target intercellular, cadherin-based junctions and contribute to their formation and stability. Here, we studied the role of microtubules in conjunction with Rho-like GTPases in the regulation of lung epithelial barrier function using real-time monitoring of transepithelial electrical resistance. Unexpectedly, we found that disruption of microtubules promotes epithelial cell-cell adhesion. This increase in epithelial barrier function is accompanied by the accumulation of β-catenin at cell-cell junctions, as detected by immunofluorescence. Moreover, we found that the increase in cell-cell contact, induced by microtubule depolymerization, requires signaling through a RhoA/Rho kinase pathway. The Rac-1 GTPase counteracts this pathway, because inhibition of Rac-1 signaling rapidly promotes epithelial barrier function, in a microtubule- and RhoA-independent fashion. Together, our data suggest that microtubule-RhoA-mediated signaling and Rac-1 control lung epithelial integrity through counteracting independent pathways.

scholarly journals Cortical actin flow activates an alpha-catenin clutch to assemble adherens junctions

2021 ◽  
Author(s):  
Ivar Noordstra ◽  
Mario Diez Hermoso ◽  
Lilian Schimmel ◽  
Alexis Bonfim-Melo ◽  
Joseph Mathew Kalappurakkal ◽  
...  
Keyword(s):  
Adherens Junctions ◽  
Actin Binding ◽  
Cell Contact ◽  
Cortical Actin ◽  
Bond Behaviour ◽  
Catch Bond ◽  
Actin Cortex ◽  
Mediate Cell ◽  
E Cadherin ◽  
Cell Cell

Adherens junctions (AJs) fundamentally mediate cell-cell adhesion, yet the mechanisms that determine where or when AJs assemble are not understood. Here we reveal a mechanosensitive clutch that initiates AJ assembly. Before cell-cell contact, alpha-catenin couples surface E-cadherin complexes to retrograde flow of the actin cortex. Cortical flows with opposed orientations persist after contact, applying tension to alpha-catenin within trans-ligated cadherin complexes. Tension unfolds the alpha-catenin actin-binding domain (ABD), which is expected to mediate a catch bond with F-actin. However, catch bond behaviour is not sufficient for AJ assembly in a molecular clutch model. Instead, it is also necessary for the activated ABD to promote cis-clustering of E-cadherin molecules by bundling F-actin. Thus, this alpha-catenin clutch transduces the mechanical signal of cortical flow to assemble AJs.

scholarly journals The multifarious regulation of the apical junctional complex

Open Biology ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 190278 ◽  
Author(s):  
Alexandra D. Rusu ◽  
Marios Georgiou
Keyword(s):  
Cell Adhesion ◽  
Cell Junctions ◽  
Junctional Complex ◽  
Tissue Architecture ◽  
Comprehensive Overview ◽  
Cell Behaviour ◽  
Apical Junctional Complex ◽  
Mediate Cell ◽  
And Function ◽  
Cell Cell

Epithelial cells form highly organized polarized sheets with characteristic cell morphologies and tissue architecture. Cell–cell adhesion and intercellular communication are prerequisites of such cohesive sheets of cells, and cell connectivity is mediated through several junctional assemblies, namely desmosomes, adherens, tight and gap junctions. These cell–cell junctions form signalling hubs that not only mediate cell–cell adhesion but impact on multiple aspects of cell behaviour, helping to coordinate epithelial cell shape, polarity and function. This review will focus on the tight and adherens junctions, constituents of the apical junctional complex, and aims to provide a comprehensive overview of the complex signalling that underlies junction assembly, integrity and plasticity.

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.

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