Hyper-adhesion: a new concept in cell–cell adhesion

2008 ◽  
Vol 36 (2) ◽  
pp. 195-201 ◽  
Author(s):  
David Garrod ◽  
Tomomi E. Kimura
Keyword(s):  
Molecular Structure ◽  
Cell Adhesion ◽  
Molecular Basis ◽  
Cell Signalling ◽  
Binding Interaction ◽  
Wound Edge ◽  
Desmosomal Cadherins ◽  
Kinase C ◽  
Strong Adhesion ◽  
Cell Cell

We have developed a new concept of cell–cell adhesion termed ‘hyper-adhesion’, the very strong adhesion adopted by desmosomes. This uniquely desmosomal property accounts for their ability to provide the intercellular links in the desmosome–intermediate filament complex. These links are targeted by diseases, resulting in disruption of the complex with severe consequences. Hyper-adhesion is characteristic of desmosomes in tissues and is believed to result from a highly ordered arrangement of the extracellular domains of the desmosomal cadherins that locks their binding interaction so that it is highly resistant to disruption. This ordered arrangement may be reflected by and dependent upon a similarly ordered molecular structure of the desmosomal plaque. Hyper-adhesion can be down-regulated to a more weakly adhesive state by cell signalling involving protein kinase C, which translocates to the desmosomal plaque. Down-regulation takes place in wound edge epithelium and appears to be accompanied by loss of the ordered arrangement causing desmosomes to adopt the type of weaker adhesion characteristic of adherens junctions. We review the evidence for hyper-adhesion and speculate on the molecular basis of its mechanism.

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.

scholarly journals Direct Ca2+-dependent Heterophilic Interaction between Desmosomal Cadherins, Desmoglein and Desmocollin, Contributes to Cell–Cell Adhesion

1997 ◽  
Vol 138 (1) ◽  
pp. 193-201 ◽  
Author(s):  
Nikolai A. Chitaev ◽  
Sergey M. Troyanovsky
Keyword(s):  
Cell Adhesion ◽  
Solid Phase ◽  
Adherens Junctions ◽  
Deletion Mapping ◽  
Dependent Manner ◽  
Intercellular Interaction ◽  
Desmosomal Cadherins ◽  
Human Fibrosarcoma Cells ◽  
A Minor ◽  
Cell Cell

Human fibrosarcoma cells, HT-1080, feature extensive adherens junctions, lack mature desmosomes, and express a single known desmosomal protein, Desmoglein 2 (Dsg2). Transfection of these cells with bovine Desmocollin 1a (Dsc1a) caused dramatic changes in the subcellular distribution of endogenous Dsg2. Both cadherins clustered in the areas of the adherens junctions, whereas only a minor portion of Dsg2 was seen in these areas in the parental cells. Deletion mapping showed that intact extracellular cadherin-like repeats of Dsc1a (Arg1-Thr170) are required for the translocation of Dsg2. Deletion of the intracellular C-domain that mediates the interaction of Dsc1a with plakoglobin, or the CSI region that is involved in the binding to desmoplakin, had no effect. Coimmunoprecipitation experiments of cell lysates stably expressing Dsc1a with anti-Dsc or -Dsg antibodies demonstrate that the desmosomal cadherins, Dsg2 and Dsc1a, are involved in a direct Ca2+-dependent interaction. This conclusion was further supported by the results of solid phase binding experiments. These showed that the Dsc1a fragment containing cadherin-like repeats 1 and 2 binds directly to the extracellular portion of Dsg in a Ca2+-dependent manner. The contribution of the Dsg/ Dsc interaction to cell–cell adhesion was tested by coculturing HT-1080 cells expressing Dsc1a with HT-1080 cells lacking Dsc but expressing myc-tagged plakoglobin (MPg). In the latter cells, MPg and the endogenous Dsg form stable complexes. The observed specific coimmunoprecipitation of MPg by anti-Dsc antibodies in coculture indicates that an intercellular interaction between Dsc1 and Dsg is involved in cell–cell adhesion.

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 CD151 regulates epithelial cell–cell adhesion through PKC- and Cdc42-dependent actin cytoskeletal reorganization

2003 ◽  
Vol 163 (1) ◽  
pp. 165-176 ◽  
Author(s):  
Masaki Shigeta ◽  
Noriko Sanzen ◽  
Masayuki Ozawa ◽  
Jianguo Gu ◽  
Hitoshi Hasegawa ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Cytoskeletal Reorganization ◽  
Cortical Actin ◽  
A431 Cells ◽  
Kinase C ◽  
Integrin Α3β1 ◽  
E Cadherin ◽  
Cell Cell

CD151, a member of the tetraspanin family proteins, tightly associates with integrin α3β1 and localizes at basolateral surfaces of epithelial cells. We found that overexpression of CD151 in A431 cells accelerated intercellular adhesion, whereas treatment of cells with anti-CD151 mAb perturbed the integrity of cortical actin filaments and cell polarity. E-Cadherin puncta formation, indicative of filopodia-based adhesion zipper formation, as well as E-cadherin anchorage to detergent-insoluble cytoskeletal matrix, was enhanced in CD151-overexpressing cells. Levels of GTP-bound Cdc42 and Rac were also elevated in CD151-overexpressing cells, suggesting the role of CD151 in E-cadherin–mediated cell–cell adhesion as a modulator of actin cytoskeletal reorganization. Consistent with this possibility, engagement of CD151 by the substrate-adsorbed anti-CD151 mAb induced prominent Cdc42-dependent filopodial extension, which along with E-cadherin puncta formation, was strongly inhibited by calphostin C, a protein kinase C (PKC) inhibitor. Together, these results indicate that CD151 is involved in epithelial cell–cell adhesion as a modulator of PKC- and Cdc42-dependent actin cytoskeletal reorganization.

scholarly journals Protein Kinase C Activation Upregulates Intercellular Adhesion of α-Catenin–negative Human Colon Cancer Cell Variants via Induction of Desmosomes

1997 ◽  
Vol 137 (5) ◽  
pp. 1103-1116 ◽  
Author(s):  
Jolanda van Hengel ◽  
Lionel Gohon ◽  
Erik Bruyneel ◽  
Stefan Vermeulen ◽  
Maria Cornelissen ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Human Colon ◽  
Intercellular Adhesion ◽  
Human Colon Cancer ◽  
Human Colon Carcinoma Cell ◽  
Kinase C ◽  
E Cadherin ◽  
Cell Cell

The α-catenin molecule links E-cadherin/ β-catenin or E-cadherin/plakoglobin complexes to the actin cytoskeleton. We studied several invasive human colon carcinoma cell lines lacking α-catenin. They showed a solitary and rounded morphotype that correlated with increased invasiveness. These round cell variants acquired a more normal epithelial phenotype upon transfection with an α-catenin expression plasmid, but also upon treatment with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Video registrations showed that the cells started to establish elaborated intercellular junctions within 30 min after addition of TPA. Interestingly, this normalizing TPA effect was not associated with α-catenin induction. Classical and confocal immunofluorescence showed only minor TPA-induced changes in E-cadherin staining. In contrast, desmosomal and tight junctional proteins were dramatically rearranged, with a conversion from cytoplasmic clusters to obvious concentration at cell–cell contacts and exposition at the exterior cell surface. Electron microscopical observations revealed the TPA-induced appearance of typical desmosomal plaques. TPA-restored cell–cell adhesion was E-cadherin dependent as demonstrated by a blocking antibody in a cell aggregation assay. Addition of an antibody against the extracellular part of desmoglein-2 blocked the TPA effect, too. Remarkably, the combination of anti–E-cadherin and anti-desmoglein antibodies synergistically inhibited the TPA effect. Our studies show that it is possible to bypass the need for normal α-catenin expression to establish tight intercellular adhesion by epithelial cells. Apparently, the underlying mechanism comprises upregulation of desmosomes and tight junctions by activation of the PKC signaling pathway, whereas E-cadherin remains essential for basic cell–cell adhesion, even in the absence of α-catenin.

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.

Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion

1998 ◽  
Vol 111 (4) ◽  
pp. 495-509 ◽  
Author(s):  
C. Marcozzi ◽  
I.D. Burdett ◽  
R.S. Buxton ◽  
A.I. Magee
Keyword(s):  
Cell Adhesion ◽  
Intercellular Junctions ◽  
Cell Aggregation ◽  
Cell Contact ◽  
Desmosomal Cadherins ◽  
Contact Sites ◽  
L Cells ◽  
Classical Cadherins ◽  
Adhesion Activity ◽  
Cell Cell

Desmosomes are unique intercellular junctions in that they invariably contain two types of transmembrane cadherin molecule, desmocollins and desmogleins. In addition they possess a distinct cytoplasmic plaque structure containing a few major proteins including desmoplakins and the armadillo family member plakoglobin. Desmosomal cadherins are putative cell-cell adhesion molecules and we have tested their adhesive capacity using a transfection approach in mouse L cells. We find that L cells expressing either one or both of the desmosomal cadherins desmocollin 2a or desmoglein 1 display weak cell-cell adhesion activity that is Ca2+-dependent. Both homophilic and heterophilic adhesion could be detected. However, co-expression of plakoglobin with both desmosomal cadherins, but not with desmoglein 1 alone, resulted in a dramatic potentiation of cell-cell aggregation and the accumulation of detergent-insoluble desmosomal proteins at points of cell-cell contact. The effect of plakoglobin seems to be due directly to its interaction with the desmosomal cadherins rather than to its signalling function. The data suggest that the desmosome may obligatorily contain two cadherins and is consistent with a model in which desmocollins and desmogleins may form side by side heterodimers in contrast to the classical cadherins that are homodimeric. Plakoglobin may function by potentiating dimer formation, accretion of dimers to cell-cell contact sites or desmosomal cadherin stability.

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