scholarly journals Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity

2018 ◽  
Author(s):  
K. Venkatesan Iyer ◽  
Romina Piscitello-Gómez ◽  
Frank Jülicher ◽  
Suzanne Eaton
Keyword(s):  
Mechanical Stress ◽  
High Stress ◽  
Mechanical Stresses ◽  
Cell Junctions ◽  
Epithelial Tissue ◽  
Viscoelastic Deformation ◽  
P120 Catenin ◽  
Pupal Wing ◽  
Shape Changes ◽  
E Cadherin

AbstractStudying how epithelia respond to mechanical stresses is key to understanding tissue shape changes during morphogenesis. Here, we study the viscoelastic deformation of the Drosophila pupal wing epithelium in response to mechanical stress that evolves during morphogenesis. We show that wing epithelial tissue viscoelasticity depends on endocytic turnover of E-Cadherin. The fraction of ECadherin undergoing turnover depends on mechanical stress in the epithelium. We identified mechanosensitive binding of the endocytic regulator p120-Catenin (p120) as a mechanism to regulate E-Cadherin turnover. Under high stress, p120 is released into the cytoplasm, destabilizing E-Cadherin complexes and increasing its turnover. In p120 mutants, E-Cadherin turnover is insensitive to mechanical stress. Furthermore, we show that p120 is crucial for the viscoelastic deformation of the wing epithelium. Taken together, our findings reveal that mechanosensitive binding of p120-Catenin tunes epithelial tissue viscoelasticity during morphogenesis.

DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading

2009 ◽  
Vol 297 (2) ◽  
pp. C419-C429 ◽  
Author(s):  
Chau-Zen Wang ◽  
Yi-Chun Yeh ◽  
Ming-Jer Tang
Keyword(s):  
Small Interfering Rna ◽  
Cell Spreading ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cell Behavior ◽  
P120 Catenin ◽  
Discoidin Domain Receptors ◽  
Collagen Receptors ◽  
Interfering Rna ◽  
E Cadherin

Discoidin domain receptors (DDRs) 1 and 2, collagen receptors, regulate cell adhesion and a broad range of cell behavior. Their adhesion-dependent regulation of signaling associated with adhesion proteins has not been elucidated. We report a novel mechanism: the cross talk of DDR1 and E-cadherin negatively and adhesion dependently regulated both DDR1 activity and DDR1-suppressed cell spreading. E-cadherin forms complexes with both DDR1 isoforms (a and b). E-cadherin regulates DDR1 activity associated with the cell-junction complexes formed between DDR1 and E-cadherin. These complexes are formed independently of DDR1 activation and of β-catenin and p120-catenin binding to E-cadherin; they are ubiquitous in epithelial cells. Small interfering RNA-mediated gene silencing of E-cadherin restores both DDR1 activity and DDR1-suppressed cell spreading and increases the apically and basally located DDR1 in E-cadherin-null cells. We conclude that E-cadherin-mediated adhesions decrease DDR1 activity, which subsequently eliminates DDR1-suppressed cell spreading, by sequestering DDR1 to cell junctions, which prevents its contact with collagen ligand.

Silvicultural control of mechanical stresses in trees

1988 ◽  
Vol 18 (10) ◽  
pp. 1215-1225 ◽  
Author(s):  
Hans Kubler
Keyword(s):  
Spatial Distribution ◽  
Mechanical Stress ◽  
High Stress ◽  
Growth Conditions ◽  
Mechanical Stresses ◽  
Reaction Wood ◽  
Prevailing Wind ◽  
Growth Stresses ◽  
Stable Growth ◽  
Steep Slopes

Mechanical stress generated by growing wood cells causes heart checks in the ends of timber, while lumber end-splits and warps. It is not possible to prevent these growth stresses but they can be minimized. Trees generate relatively high stress in order to bend stems and branches into positions more favorable for the tree, as is known from reaction wood, whose growth stresses are extremely high. One controls the stresses by giving trees no reason to reorient themselves, that is, by providing stable growth conditions. To this end, trees should have sufficient, uniform light, and where light is scarce, as in understories, one-sided light changes have to be avoided. In particular, the spatial distribution of trees in the stand should be uniform; multistoried forests are preferable to single-storied, even-aged plantations. The stands should be thinned slightly, frequently, and uniformly, rather than haphazardly and severely after long periods. In areas with strong prevailing wind, close spacing may minimize the stresses, whereas on steep slopes wide spacing appears to be preferable.

scholarly journals Formin-mediated actin polymerization at cell–cell junctions stabilizes E-cadherin and maintains monolayer integrity during wound repair

2016 ◽  
Vol 27 (18) ◽  
pp. 2844-2856 ◽  
Author(s):  
Megha Vaman Rao ◽  
Ronen Zaidel-Bar
Keyword(s):  
Cell Adhesion ◽  
Wound Repair ◽  
Actin Polymerization ◽  
Cell Junctions ◽  
Epithelial Tissue ◽  
Collective Cell Migration ◽  
Epithelial Junctions ◽  
Major Factors ◽  
E Cadherin ◽  
Cell Cell

Cadherin-mediated cell–cell adhesion is required for epithelial tissue integrity in homeostasis, during development, and in tissue repair. E-cadherin stability depends on F-actin, but the mechanisms regulating actin polymerization at cell–cell junctions remain poorly understood. Here we investigated a role for formin-mediated actin polymerization at cell–cell junctions. We identify mDia1 and Fmnl3 as major factors enhancing actin polymerization and stabilizing E-cadherin at epithelial junctions. Fmnl3 localizes to adherens junctions downstream of Src and Cdc42 and its depletion leads to a reduction in F-actin and E-cadherin at junctions and a weakening of cell–cell adhesion. Of importance, Fmnl3 expression is up-regulated and junctional localization increases during collective cell migration. Depletion of Fmnl3 or mDia1 in migrating monolayers results in dissociation of leader cells and impaired wound repair. In summary, our results show that formin activity at epithelial cell–cell junctions is important for adhesion and the maintenance of epithelial cohesion during dynamic processes, such as wound repair.

scholarly journals Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction

2016 ◽  
Vol 113 (51) ◽  
pp. 14698-14703 ◽  
Author(s):  
Daniel J. Cohen ◽  
Martijn Gloerich ◽  
W. James Nelson
Keyword(s):  
Epithelial Cell ◽  
Vertical Surface ◽  
Stop Signal ◽  
Cell Junctions ◽  
Epithelial Tissue ◽  
Self Healing ◽  
Material Interfaces ◽  
Cell Adhesions ◽  
E Cadherin ◽  
Cell Cell

Epithelial monolayers undergo self-healing when wounded. During healing, cells collectively migrate into the wound site, and the converging tissue fronts collide and form a stable interface. To heal, migrating tissues must form cell–cell adhesions and reorganize from the front-rear polarity characteristic of cell migration to the apical-basal polarity of an epithelium. However, identifying the "stop signal" that induces colliding tissues to cease migrating and heal remains an open question. Epithelial cells form integrin-based adhesions to the basal extracellular matrix (ECM) and E-cadherin–mediated cell–cell adhesions on the orthogonal, lateral surfaces between cells. Current biological tools have been unable to probe this multicellular 3D interface to determine the stop signal. We addressed this problem by developing a unique biointerface that mimicked the 3D organization of epithelial cell adhesions. This "minimal tissue mimic" (MTM) comprised a basal ECM substrate and a vertical surface coated with purified extracellular domain of E-cadherin, and was designed for collision with the healing edge of an epithelial monolayer. Three-dimensional imaging showed that adhesions formed between cells, and the E-cadherin-coated MTM resembled the morphology and dynamics of native epithelial cell–cell junctions and induced the same polarity transition that occurs during epithelial self-healing. These results indicate that E-cadherin presented in the proper 3D context constitutes a minimum essential stop signal to induce self-healing. That the Ecad:Fc MTM stably integrated into an epithelial tissue and reduced migration at the interface suggests that this biointerface is a complimentary approach to existing tissue–material interfaces.

scholarly journals Transition of responsive mechanosensitive elements from focal adhesions to adherens junctions on epithelial differentiation

2018 ◽  
Vol 29 (19) ◽  
pp. 2317-2325 ◽  
Author(s):  
Barbara Noethel ◽  
Lena Ramms ◽  
Georg Dreissen ◽  
Marco Hoffmann ◽  
Ronald Springer ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Adherens Junctions ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Intercellular Junctions ◽  
Cell Junctions ◽  
Epithelial Tissue ◽  
Cell Matrix ◽  
Junction Protein ◽  
Cell Cell

The skin’s epidermis is a multilayered epithelial tissue and the first line of defense against mechanical stress. Its barrier function depends on an integrated assembly and reorganization of cell–matrix and cell–cell junctions in the basal layer and on different intercellular junctions in suprabasal layers. However, how mechanical stress is recognized and which adhesive and cytoskeletal components are involved are poorly understood. Here, we subjected keratinocytes to cyclic stress in the presence or absence of intercellular junctions. Both states not only recognized but also responded to strain by reorienting actin filaments perpendicular to the applied force. Using different keratinocyte mutant strains that altered the mechanical link of the actin cytoskeleton to either cell–matrix or cell–cell junctions, we show that not only focal adhesions but also adherens junctions function as mechanosensitive elements in response to cyclic strain. Loss of paxillin or talin impaired focal adhesion formation and only affected mechanosensitivity in the absence but not presence of intercellular junctions. Further analysis revealed the adherens junction protein α-catenin as a main mechanosensor, with greatest sensitivity conferred on binding to vinculin. Our data reveal a mechanosensitive transition from cell–matrix to cell–cell adhesions on formation of keratinocyte monolayers with vinculin and α-catenin as vital players.

scholarly journals DISTINCT ACTIN-DEPENDENT NANOSCALE ASSEMBLIES UNDERLIE THE DYNAMIC AND HIERARCHICAL ORGANIZATION OF E-CADHERIN

2019 ◽  
Author(s):  
Rumamol Chandran ◽  
Girish Kale ◽  
Jean-Marc Philippe ◽  
Thomas Lecuit ◽  
Satyajit Mayor
Keyword(s):  
Ectopic Expression ◽  
Fluorescence Emission ◽  
Correlation Spectroscopy ◽  
Hierarchical Organization ◽  
Cell Junctions ◽  
Epithelial Tissue ◽  
Emission Anisotropy ◽  
Dynamic Organization ◽  
E Cadherin ◽  
Cell Cell

SUMMARYIntercellular adhesion mediated by E-cadherin is pivotal in maintaining epithelial tissue integrity and for tissue morphogenesis. Adhesion requires homophilic interactions between extracellular domains of E-cadherin molecules from neighboring cells. The interaction of its cytoplasmic domains with the cortical acto-myosin network, appears to strengthen adhesion, although, it is unclear how cortical actin affects the organization and function of E-cadherin dynamically. Here we use the ectopic expression of Drosophila E-cadherin (E-cad) in larval hemocytes, which lack endogenous E-cad, to recapitulate functional cell-cell junctions in a convenient model system. We used fluorescence emission anisotropy-based microscopy and Fluorescence Correlation Spectroscopy (FCS) to probe the nanoscale organization of E-cad. We find that E-cad at cell-cell junctions in hemocytes exhibits a clustered trans-paired organization, similar to that reported for the adherens junction in the developing embryonic epithelial tissue. Further, we find that extra-junctional E-cad is also organized as relatively immobile nanoclusters as well as diffusive and more loosely packed oligomers and monomers. These oligomers are promoted by cis-interactions of the ectodomain and, strikingly, their growth is constantly counteracted by cortical actomyosin. Oligomers in turn assist in generating nanoclusters that are stabilized by cortical acto-myosin. Thus, actin remodels oligomers and stabilizes nanoclusters, revealing a requirement for actin in the dynamic organization of E-cad at the nanoscale. This dynamic organization is also present at cell-cell contacts (junction), and its disruption affects junctional integrity in the hemocyte system, as well as in the embryo. Our observations uncover a hierarchical mechanism for the nanoscale organization of E-cad, which is necessary for dynamic adhesion and maintaining junctional integrity in the face of extensive remodeling.

scholarly journals Interplay between cortical actin and E-cadherin dynamics regulates cell shape in the Drosophila embryonic epidermis

2019 ◽  
Author(s):  
Joshua Greig ◽  
Natalia A. Bulgakova
Keyword(s):  
Cell Adhesion ◽  
Cell Elongation ◽  
Cell Shape ◽  
Intercellular Adhesion ◽  
Epithelial Tissue ◽  
Cortical Actin ◽  
P120 Catenin ◽  
Endocytic Machinery ◽  
E Cadherin

AbstractPrecise regulation of cell shape is vital for building functional tissues. Here, we study the mechanisms which lead to the formation of highly elongated anisotropic epithelial cells in the Drosophila epidermis. We demonstrate that this cell shape is the result of two counteracting mechanisms at the cell surface: actomyosin, which inhibits cell elongation downstream of RhoA signalling, and intercellular adhesion, modulated via clathrin-mediated endocytosis of E-cadherin, which promotes cell elongation downstream of the GTPase Arf1. We show that these two mechanisms are interconnected, with RhoA signalling activity reducing Arf1 recruitment to the plasma membrane. Additionally, cell adhesion itself regulates both mechanisms: p120-catenin, a regulator of intercellular adhesion, promotes the activity of both Arf1 and RhoA. Altogether, we uncover a complex network of interactions between cell-cell adhesion, the endocytic machinery, and the actomyosin cortex, and demonstrate how this network regulates cell shape in an epithelial tissue in vivo.

p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion

2001 ◽  
Vol 114 (4) ◽  
pp. 695-707 ◽  
Author(s):  
I. Grosheva ◽  
M. Shtutman ◽  
M. Elbaum ◽  
A.D. Bershadsky
Keyword(s):  
Cell Motility ◽  
Small Gtpases ◽  
Cell Junctions ◽  
P120 Catenin ◽  
Contact Formation ◽  
Cell Locomotion ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
E Cadherin ◽  
Cell Cell

The molecular basis for contact inhibition of cell locomotion is still largely unknown. Cadherins, the major receptors mediating cell-cell adhesion, associate in the cytoplasm with armadillo family proteins, including beta- and gamma-catenin and p120 catenin (p120ctn). E-cadherin-mediated contact formation was shown to inhibit cellular motility. We examine whether p120ctn may have a role in this regulation. We show here that overexpression of p120ctn in fibroblasts and epithelial cells induces pronounced changes in cell shape, motility and adhesion to the extracellular matrix. p120ctn-transfected cells display increased filopodial/lamellipodial activity, decreased contractility and focal adhesion formation, and augmented migratory ability. These effects of p120ctn are mediated by small GTPases of the Rho family. Direct assessment of the activity of these GTPases in cells expressing a 5-fold higher level of p120ctn as compared to non-transfected control cells revealed significant augmentation of Cdc42 and Rac activity. Moreover, co-transfection of p120ctn with dominant-negative Cdc42 and Rac, or constitutively active Rho suppressed morphological effects of p120ctn. Confocal immunofluorescence visualization of the distribution of endogenous p120ctn in dense cultures showed that formation of cadherin-mediated cell-cell contacts is accompanied by sequestering of p120ctn to the junction regions. In sparse cultures p120ctn is distributed over the cytoplasm. Co-transfection with an excess of E-cadherin leads to sequestration of exogenous p120ctn to cell-cell junctions or to small cadherin-containing vesicles, and abolishes p120ctn effects on cell morphology. Thus, p120ctn may couple the formation and disruption of cadherin-mediated contacts with regulation of cell motility by triggering pathway(s) affecting Rho family GTPases.

scholarly journals Interplay between actomyosin and E-cadherin dynamics regulates cell shape in the Drosophila embryonic epidermis

2020 ◽  
Vol 133 (15) ◽  
pp. jcs242321
Author(s):  
Joshua Greig ◽  
Natalia A. Bulgakova
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Cell Elongation ◽  
Cell Shape ◽  
Intercellular Adhesion ◽  
Epithelial Tissue ◽  
P120 Catenin ◽  
Endocytic Machinery ◽  
E Cadherin

ABSTRACTPrecise regulation of cell shape is vital for building functional tissues. Here, we study the mechanisms that lead to the formation of highly elongated anisotropic epithelial cells in the Drosophila epidermis. We demonstrate that this cell shape is the result of two counteracting mechanisms at the cell surface that regulate the degree of elongation: actomyosin, which inhibits cell elongation downstream of RhoA (Rho1 in Drosophila) and intercellular adhesion, modulated via clathrin-mediated endocytosis of E-cadherin (encoded by shotgun in flies), which promotes cell elongation downstream of the GTPase Arf1 (Arf79F in Drosophila). We show that these two mechanisms do not act independently but are interconnected, with RhoA signalling reducing Arf1 recruitment to the plasma membrane. Additionally, cell adhesion itself regulates both mechanisms – p120-catenin, a regulator of intercellular adhesion, promotes the activity of both Arf1 and RhoA. Altogether, we uncover a complex network of interactions between cell–cell adhesion, the endocytic machinery and the actomyosin cortex, and demonstrate how this network regulates cell shape in an epithelial tissue in vivo.

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